anno_start	anno_end	anno_text	entity_type	sentence	section
0	19	Hemi-methylated DNA	chemical	Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition	TITLE
28	34	closed	protein_state	Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition	TITLE
51	56	UHRF1	protein	Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition	TITLE
75	82	histone	protein_type	Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition	TITLE
0	5	UHRF1	protein	UHRF1 is an important epigenetic regulator for maintenance DNA methylation.	ABSTRACT
63	74	methylation	ptm	UHRF1 is an important epigenetic regulator for maintenance DNA methylation.	ABSTRACT
0	5	UHRF1	protein	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
17	36	hemi-methylated DNA	chemical	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
38	44	hm-DNA	chemical	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
50	64	trimethylation	ptm	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
68	75	histone	protein_type	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
76	78	H3	protein_type	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
78	80	K9	residue_name_number	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
82	84	H3	protein_type	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
84	89	K9me3	ptm	UHRF1 recognizes hemi-methylated DNA (hm-DNA) and trimethylation of histone H3K9 (H3K9me3), but the regulatory mechanism remains unknown.	ABSTRACT
18	23	UHRF1	protein	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
33	39	closed	protein_state	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
65	82	C-terminal region	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
84	90	Spacer	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
92	100	binds to	protein_state	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
105	124	tandem Tudor domain	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
126	129	TTD	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
144	146	H3	protein_type	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
146	151	K9me3	ptm	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
177	200	SET-and-RING-associated	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
202	205	SRA	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
214	222	binds to	protein_state	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
227	244	plant homeodomain	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
246	249	PHD	structure_element	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
264	268	H3R2	site	Here we show that UHRF1 adopts a closed conformation, in which a C-terminal region (Spacer) binds to the tandem Tudor domain (TTD) and inhibits H3K9me3 recognition, whereas the SET-and-RING-associated (SRA) domain binds to the plant homeodomain (PHD) and inhibits H3R2 recognition.	ABSTRACT
0	6	Hm-DNA	chemical	Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD–PHD.	ABSTRACT
60	62	H3	protein_type	Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD–PHD.	ABSTRACT
62	67	K9me3	ptm	Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD–PHD.	ABSTRACT
83	90	TTD–PHD	structure_element	Hm-DNA impairs the intramolecular interactions and promotes H3K9me3 recognition by TTD–PHD.	ABSTRACT
4	10	Spacer	structure_element	The Spacer also facilitates UHRF1–DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA.	ABSTRACT
28	39	UHRF1–DNMT1	complex_assembly	The Spacer also facilitates UHRF1–DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA.	ABSTRACT
65	88	hm-DNA-binding affinity	evidence	The Spacer also facilitates UHRF1–DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA.	ABSTRACT
96	99	SRA	structure_element	The Spacer also facilitates UHRF1–DNMT1 interaction and enhances hm-DNA-binding affinity of the SRA.	ABSTRACT
5	12	TTD–PHD	structure_element	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
13	21	binds to	protein_state	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
22	24	H3	protein_type	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
24	29	K9me3	ptm	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
31	41	SRA-Spacer	structure_element	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
96	102	hm-DNA	chemical	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
115	120	DNMT1	protein	When TTD–PHD binds to H3K9me3, SRA-Spacer may exist in a dynamic equilibrium: either recognizes hm-DNA or recruits DNMT1 to chromatin.	ABSTRACT
50	52	H3	protein_type	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.	ABSTRACT
52	57	K9me3	ptm	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.	ABSTRACT
62	68	hm-DNA	chemical	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.	ABSTRACT
84	89	URHF1	protein	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by URHF1.	ABSTRACT
1	6	UHRF1	protein	 UHRF1 is involved in the maintenance of DNA methylation, but the regulatory mechanism of this epigenetic regulator is unclear.	ABSTRACT
45	56	methylation	ptm	 UHRF1 is involved in the maintenance of DNA methylation, but the regulatory mechanism of this epigenetic regulator is unclear.	ABSTRACT
37	43	closed	protein_state	Here, the authors show that it has a closed conformation and are able to make conclusions about the mechanism of recognition of epigenetic marks.	ABSTRACT
4	15	methylation	ptm	DNA methylation is an important epigenetic modification for gene repression, X-chromosome inactivation, genome imprinting and maintenance of genome stability.	INTRO
0	9	Mammalian	taxonomy_domain	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
14	25	methylation	ptm	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
52	74	DNA methyltransferases	protein_type	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
75	84	DNMT3A/3B	protein	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
94	105	methylation	ptm	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
145	168	DNA methyltransferase 1	protein	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
170	175	DNMT1	protein	Mammalian DNA methylation is established by de novo DNA methyltransferases DNMT3A/3B, and DNA methylation patterns are maintained by maintenance DNA methyltransferase 1 (DNMT1) during DNA replication.	INTRO
0	58	Ubiquitin-like, containing PHD and RING fingers domains, 1	protein	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
60	65	UHRF1	protein	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
81	87	ICBP90	protein	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
92	96	NP95	protein	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
100	105	mouse	taxonomy_domain	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
153	164	methylation	ptm	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
184	189	DNMT1	protein	Ubiquitin-like, containing PHD and RING fingers domains, 1 (UHRF1, also known as ICBP90 and NP95 in mouse) was shown to be essential for maintenance DNA methylation through recruiting DNMT1 to replication forks in S phase of the cell cycle.	INTRO
0	5	UHRF1	protein	UHRF1 is essential for S phase entry and is involved in heterochromatin formation.	INTRO
0	5	UHRF1	protein	UHRF1 also plays an important role in promoting proliferation and is shown to be upregulated in a number of cancers, suggesting that UHRF1 may serve as a potential drug target for therapeutic applications.	INTRO
133	138	UHRF1	protein	UHRF1 also plays an important role in promoting proliferation and is shown to be upregulated in a number of cancers, suggesting that UHRF1 may serve as a potential drug target for therapeutic applications.	INTRO
0	5	UHRF1	protein	UHRF1 is a multi-domain containing protein connecting histone modification and DNA methylation.	INTRO
54	61	histone	protein_type	UHRF1 is a multi-domain containing protein connecting histone modification and DNA methylation.	INTRO
79	82	DNA	chemical	UHRF1 is a multi-domain containing protein connecting histone modification and DNA methylation.	INTRO
83	94	methylation	ptm	UHRF1 is a multi-domain containing protein connecting histone modification and DNA methylation.	INTRO
21	26	UHRF1	protein	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
57	78	ubiquitin-like domain	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
94	113	tandem Tudor domain	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
115	118	TTD	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
130	134	TTDN	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
139	143	TTDC	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
160	177	plant homeodomain	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
179	182	PHD	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
187	210	SET-and-RING-associated	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
212	215	SRA	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
242	269	really interesting new gene	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
271	275	RING	structure_element	As shown in Fig. 1a, UHRF1 is comprised of an N-terminal ubiquitin-like domain, followed by a tandem Tudor domain (TTD containing TTDN and TTDC sub-domains), a plant homeodomain (PHD), a SET-and-RING-associated (SRA) domain, and a C-terminal really interesting new gene (RING) domain.	INTRO
42	45	TTD	structure_element	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
54	57	PHD	structure_element	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
81	88	histone	protein_type	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
89	91	H3	protein_type	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
91	96	K9me3	ptm	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
115	117	R2	residue_name_number	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
139	142	PHD	structure_element	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
147	162	tri-methylation	ptm	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
174	176	K9	residue_name_number	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
178	183	K9me3	ptm	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
206	209	TTD	structure_element	We and other groups demonstrated that the TTD and the PHD coordinately recognize histone H3K9me3, in which residue R2 is recognized by the PHD and tri-methylation of residue K9 (K9me3) is recognized by the TTD.	INTRO
4	7	SRA	structure_element	The SRA preferentially binds to hemi-methylated DNA (hm-DNA).	INTRO
23	31	binds to	protein_state	The SRA preferentially binds to hemi-methylated DNA (hm-DNA).	INTRO
32	51	hemi-methylated DNA	chemical	The SRA preferentially binds to hemi-methylated DNA (hm-DNA).	INTRO
53	59	hm-DNA	chemical	The SRA preferentially binds to hemi-methylated DNA (hm-DNA).	INTRO
29	32	SRA	structure_element	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
42	50	binds to	protein_state	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
51	87	replication focus targeting sequence	structure_element	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
89	93	RFTS	structure_element	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
98	103	DNMT1	protein	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
105	114	RFTSDNMT1	protein	Recent studies show that the SRA directly binds to replication focus targeting sequence (RFTS) of DNMT1 (RFTSDNMT1).	INTRO
2	15	spacer region	structure_element	A spacer region (Fig. 1a, designated Spacer hereafter) connecting the SRA and the RING is rich in basic residues and predicted to be unstructured for unknown function.	INTRO
37	43	Spacer	structure_element	A spacer region (Fig. 1a, designated Spacer hereafter) connecting the SRA and the RING is rich in basic residues and predicted to be unstructured for unknown function.	INTRO
70	73	SRA	structure_element	A spacer region (Fig. 1a, designated Spacer hereafter) connecting the SRA and the RING is rich in basic residues and predicted to be unstructured for unknown function.	INTRO
82	86	RING	structure_element	A spacer region (Fig. 1a, designated Spacer hereafter) connecting the SRA and the RING is rich in basic residues and predicted to be unstructured for unknown function.	INTRO
133	145	unstructured	protein_state	A spacer region (Fig. 1a, designated Spacer hereafter) connecting the SRA and the RING is rich in basic residues and predicted to be unstructured for unknown function.	INTRO
24	54	phosphatidylinostiol phosphate	chemical	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
55	59	PI5P	chemical	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
60	68	binds to	protein_state	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
73	79	Spacer	structure_element	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
119	124	UHRF1	protein	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
138	141	TTD	structure_element	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
155	157	H3	protein_type	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
157	162	K9me3	ptm	Recent study shows that phosphatidylinostiol phosphate PI5P binds to the Spacer and induces a conformational change of UHRF1 to allow the TTD to recognize H3K9me3 (ref.).	INTRO
28	33	UHRF1	protein	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
65	68	DNA	chemical	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
69	80	methylation	ptm	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
85	87	H3	protein_type	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
87	92	K9me3	ptm	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
129	134	human	species	These studies indicate that UHRF1 connects dynamic regulation of DNA methylation and H3K9me3, which are positively correlated in human genome.	INTRO
13	18	UHRF1	protein	However, how UHRF1 regulates the recognition of these two repressive epigenetic marks and recruits DNMT1 for chromatin localization remain largely unknown.	INTRO
99	104	DNMT1	protein	However, how UHRF1 regulates the recognition of these two repressive epigenetic marks and recruits DNMT1 for chromatin localization remain largely unknown.	INTRO
20	25	UHRF1	protein	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
35	41	closed	protein_state	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
80	86	Spacer	structure_element	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
87	95	binds to	protein_state	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
100	103	TTD	structure_element	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
136	138	H3	protein_type	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
138	143	K9me3	ptm	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
157	160	SRA	structure_element	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
161	169	binds to	protein_state	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
174	177	PHD	structure_element	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
210	214	H3R2	site	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
216	228	unmethylated	protein_state	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
229	236	histone	protein_type	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
237	239	H3	protein_type	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
251	253	R2	residue_name_number	Here we report that UHRF1 adopts a closed conformation, in which the C-terminal Spacer binds to the TTD and inhibits its recognition of H3K9me3, whereas the SRA binds to the PHD and inhibits its recognition of H3R2 (unmethylated histone H3 at residue R2).	INTRO
5	15	binding to	protein_state	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
16	22	hm-DNA	chemical	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
24	29	UHRF1	protein	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
87	89	H3	protein_type	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
89	94	K9me3	ptm	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
110	117	TTD–PHD	structure_element	Upon binding to hm-DNA, UHRF1 impairs the intramolecular interactions and promotes the H3K9me3 recognition by TTD–PHD, which may further enhance its genomic localization.	INTRO
13	18	UHRF1	protein	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
36	40	open	protein_state	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
76	78	H3	protein_type	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
78	83	K9me3	ptm	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
87	94	TTD–PHD	structure_element	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
105	115	SRA-Spacer	structure_element	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
134	140	hm-DNA	chemical	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
153	158	DNMT1	protein	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
163	166	DNA	chemical	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
167	178	methylation	ptm	As a result, UHRF1 is locked in the open conformation by the association of H3K9me3 by TTD–PHD, and thus SRA-Spacer either recognizes hm-DNA or recruits DNMT1 for DNA methylation.	INTRO
11	16	UHRF1	protein	Therefore, UHRF1 may engage in a sophisticated regulation for its chromatin localization and recruitment of DNMT1 through a mechanism yet to be fully elucidated.	INTRO
108	113	DNMT1	protein	Therefore, UHRF1 may engage in a sophisticated regulation for its chromatin localization and recruitment of DNMT1 through a mechanism yet to be fully elucidated.	INTRO
50	52	H3	protein_type	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by UHRF1.	INTRO
52	57	K9me3	ptm	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by UHRF1.	INTRO
62	68	hm-DNA	chemical	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by UHRF1.	INTRO
84	89	UHRF1	protein	Our study reveals the mechanism for regulation of H3K9me3 and hm-DNA recognition by UHRF1.	INTRO
0	6	Hm-DNA	chemical	Hm-DNA facilitates histone H3K9me3 recognition by UHRF1	RESULTS
19	26	histone	protein_type	Hm-DNA facilitates histone H3K9me3 recognition by UHRF1	RESULTS
27	29	H3	protein_type	Hm-DNA facilitates histone H3K9me3 recognition by UHRF1	RESULTS
29	34	K9me3	ptm	Hm-DNA facilitates histone H3K9me3 recognition by UHRF1	RESULTS
50	55	UHRF1	protein	Hm-DNA facilitates histone H3K9me3 recognition by UHRF1	RESULTS
19	24	UHRF1	protein	To investigate how UHRF1 coordinates the recognition of H3K9me3 and hm-DNA, we purified recombinant UHRF1 (truncations and mutations) proteins from bacteria.	RESULTS
56	58	H3	protein_type	To investigate how UHRF1 coordinates the recognition of H3K9me3 and hm-DNA, we purified recombinant UHRF1 (truncations and mutations) proteins from bacteria.	RESULTS
58	63	K9me3	ptm	To investigate how UHRF1 coordinates the recognition of H3K9me3 and hm-DNA, we purified recombinant UHRF1 (truncations and mutations) proteins from bacteria.	RESULTS
68	74	hm-DNA	chemical	To investigate how UHRF1 coordinates the recognition of H3K9me3 and hm-DNA, we purified recombinant UHRF1 (truncations and mutations) proteins from bacteria.	RESULTS
100	105	UHRF1	protein	To investigate how UHRF1 coordinates the recognition of H3K9me3 and hm-DNA, we purified recombinant UHRF1 (truncations and mutations) proteins from bacteria.	RESULTS
22	46	in vitro pull-down assay	experimental_method	We first performed an in vitro pull-down assay using biotinylated histone H3 peptides and hm-DNA (Supplementary Table 1).	RESULTS
53	65	biotinylated	protein_state	We first performed an in vitro pull-down assay using biotinylated histone H3 peptides and hm-DNA (Supplementary Table 1).	RESULTS
66	73	histone	protein_type	We first performed an in vitro pull-down assay using biotinylated histone H3 peptides and hm-DNA (Supplementary Table 1).	RESULTS
74	76	H3	protein_type	We first performed an in vitro pull-down assay using biotinylated histone H3 peptides and hm-DNA (Supplementary Table 1).	RESULTS
90	96	hm-DNA	chemical	We first performed an in vitro pull-down assay using biotinylated histone H3 peptides and hm-DNA (Supplementary Table 1).	RESULTS
21	27	hm-DNA	chemical	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
69	80	full-length	protein_state	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
81	86	UHRF1	protein	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
91	103	unmethylated	protein_state	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
104	111	histone	protein_type	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
112	114	H3	protein_type	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
116	118	H3	protein_type	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
118	123	K9me0	ptm	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
128	130	H3	protein_type	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
130	135	K9me3	ptm	As shown in Fig. 1b, hm-DNA largely enhanced the interaction between full-length UHRF1 and unmethylated histone H3 (H3K9me0) or H3K9me3 peptide.	RESULTS
14	20	hm-DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
22	28	um-DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
30	42	unmethylated	protein_state	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
43	46	DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
51	57	fm-DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
59	75	fully methylated	protein_state	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
76	79	DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
144	149	UHRF1	protein	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
154	161	histone	protein_type	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
219	224	UHRF1	protein	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
233	239	hm-DNA	chemical	Compared with hm-DNA, um-DNA (unmethylated DNA) or fm-DNA (fully methylated DNA) showed marginal effect on facilitating the interaction between UHRF1 and histone peptides, which is consistent with previous studies that UHRF1 prefers hm-DNA for chromatin association (Supplementary Fig. 1a).	RESULTS
13	20	histone	protein_type	In contrast, histone peptides showed no enhancement on the interaction between hm-DNA and UHRF1 (Fig. 1c).	RESULTS
79	85	hm-DNA	chemical	In contrast, histone peptides showed no enhancement on the interaction between hm-DNA and UHRF1 (Fig. 1c).	RESULTS
90	95	UHRF1	protein	In contrast, histone peptides showed no enhancement on the interaction between hm-DNA and UHRF1 (Fig. 1c).	RESULTS
27	33	hm-DNA	chemical	These results suggest that hm-DNA facilitates histone recognition by UHRF1.	RESULTS
46	53	histone	protein_type	These results suggest that hm-DNA facilitates histone recognition by UHRF1.	RESULTS
69	74	UHRF1	protein	These results suggest that hm-DNA facilitates histone recognition by UHRF1.	RESULTS
35	38	PHD	structure_element	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
50	52	H3	protein_type	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
52	57	K9me0	ptm	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
66	69	TTD	structure_element	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
78	81	PHD	structure_element	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
92	99	TTD–PHD	structure_element	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
124	126	H3	protein_type	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
126	131	K9me3	ptm	Our previous studies show that the PHD recognizes H3K9me0 and the TTD and the PHD together (TTD–PHD) coordinately recognize H3K9me3 (refs.).	RESULTS
20	28	isolated	protein_state	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
29	36	TTD–PHD	structure_element	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
67	83	binding affinity	evidence	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
87	89	H3	protein_type	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
89	94	K9me3	ptm	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
108	119	full-length	protein_state	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
120	125	UHRF1	protein	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
180	183	PHD	structure_element	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
214	230	binding affinity	evidence	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
234	236	H3	protein_type	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
236	241	K9me0	ptm	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
255	266	full-length	protein_state	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
267	272	UHRF1	protein	We noticed that the isolated TTD–PHD showed much higher (∼31-fold) binding affinity to H3K9me3 peptide than full-length UHRF1 (Fig. 1d and Supplementary Table 2), and the isolated PHD showed much higher (∼34-fold) binding affinity to H3K9me0 peptide than full-length UHRF1 (Fig. 1e).	RESULTS
4	27	gel filtration analysis	experimental_method	The gel filtration analysis showed that UHRF1 is a monomer in solution (Supplementary Fig. 1b), indicating that the intramolecular (not intermolecular) interaction of UHRF1 regulates histone recognition.	RESULTS
40	45	UHRF1	protein	The gel filtration analysis showed that UHRF1 is a monomer in solution (Supplementary Fig. 1b), indicating that the intramolecular (not intermolecular) interaction of UHRF1 regulates histone recognition.	RESULTS
51	58	monomer	oligomeric_state	The gel filtration analysis showed that UHRF1 is a monomer in solution (Supplementary Fig. 1b), indicating that the intramolecular (not intermolecular) interaction of UHRF1 regulates histone recognition.	RESULTS
167	172	UHRF1	protein	The gel filtration analysis showed that UHRF1 is a monomer in solution (Supplementary Fig. 1b), indicating that the intramolecular (not intermolecular) interaction of UHRF1 regulates histone recognition.	RESULTS
183	190	histone	protein_type	The gel filtration analysis showed that UHRF1 is a monomer in solution (Supplementary Fig. 1b), indicating that the intramolecular (not intermolecular) interaction of UHRF1 regulates histone recognition.	RESULTS
27	32	UHRF1	protein	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
73	80	histone	protein_type	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
81	83	H3	protein_type	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
112	119	TTD–PHD	structure_element	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
157	162	UHRF1	protein	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
168	174	hm-DNA	chemical	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
248	255	histone	protein_type	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
256	258	H3	protein_type	These results suggest that UHRF1 adopts an unfavourable conformation for histone H3 tails recognition, in which TTD–PHD might be blocked by other regions of UHRF1, and hm-DNA impairs this intramolecular interaction to facilitate its recognition of histone H3 tails.	RESULTS
34	39	UHRF1	protein	Intramolecular interaction within UHRF1	RESULTS
39	86	glutathione S-transferase (GST) pull-down assay	experimental_method	To test above hypothesis, we performed glutathione S-transferase (GST) pull-down assay using various truncations of UHRF1.	RESULTS
101	112	truncations	experimental_method	To test above hypothesis, we performed glutathione S-transferase (GST) pull-down assay using various truncations of UHRF1.	RESULTS
116	121	UHRF1	protein	To test above hypothesis, we performed glutathione S-transferase (GST) pull-down assay using various truncations of UHRF1.	RESULTS
19	22	TTD	structure_element	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
32	40	bound to	protein_state	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
41	51	SRA-Spacer	structure_element	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
64	67	SRA	structure_element	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
89	95	Spacer	structure_element	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
106	113	587–674	residue_range	Interestingly, the TTD directly bound to SRA-Spacer but not the SRA, suggesting that the Spacer (residues 587–674) is important for the intramolecular interaction (Fig. 2a).	RESULTS
4	36	isothermal titration calorimetry	experimental_method	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
38	41	ITC	experimental_method	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
70	73	TTD	structure_element	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
74	82	bound to	protein_state	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
87	93	Spacer	structure_element	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
107	110	SRA	structure_element	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
142	158	binding affinity	evidence	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
160	162	KD	evidence	The isothermal titration calorimetry (ITC) measurements show that the TTD bound to the Spacer (but not the SRA) in a 1:1 stoichiometry with a binding affinity (KD) of 1.59 μM (Fig. 2b).	RESULTS
4	15	presence of	protein_state	The presence of the Spacer markedly impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
20	26	Spacer	structure_element	The presence of the Spacer markedly impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
69	76	TTD–PHD	structure_element	The presence of the Spacer markedly impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
81	83	H3	protein_type	The presence of the Spacer markedly impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
83	88	K9me3	ptm	The presence of the Spacer markedly impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
30	36	Spacer	structure_element	The results indicate that the Spacer directly binds to the TTD and inhibits its interaction with H3K9me3.	RESULTS
46	54	binds to	protein_state	The results indicate that the Spacer directly binds to the TTD and inhibits its interaction with H3K9me3.	RESULTS
59	62	TTD	structure_element	The results indicate that the Spacer directly binds to the TTD and inhibits its interaction with H3K9me3.	RESULTS
97	99	H3	protein_type	The results indicate that the Spacer directly binds to the TTD and inhibits its interaction with H3K9me3.	RESULTS
99	104	K9me3	ptm	The results indicate that the Spacer directly binds to the TTD and inhibits its interaction with H3K9me3.	RESULTS
4	23	GST pull-down assay	experimental_method	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
44	47	PHD	structure_element	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
48	56	bound to	protein_state	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
61	64	SRA	structure_element	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
101	104	ITC	experimental_method	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
119	121	KD	evidence	The GST pull-down assay also shows that the PHD bound to the SRA, which was further confirmed by the ITC measurements (KD=26.7 μM; Fig. 2a,d).	RESULTS
18	21	PHD	structure_element	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
22	27	alone	protein_state	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
29	36	PHD-SRA	structure_element	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
54	70	binding affinity	evidence	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
74	76	H3	protein_type	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
76	81	K9me0	ptm	Compared with the PHD alone, PHD-SRA showed decreased binding affinity to H3K9me0 peptide by a factor of eight (Fig. 2e).	RESULTS
0	14	Pre-incubation	experimental_method	Pre-incubation of the SRA also modestly impaired PHD–H3K9me0 interaction.	RESULTS
22	25	SRA	structure_element	Pre-incubation of the SRA also modestly impaired PHD–H3K9me0 interaction.	RESULTS
49	52	PHD	structure_element	Pre-incubation of the SRA also modestly impaired PHD–H3K9me0 interaction.	RESULTS
53	55	H3	protein_type	Pre-incubation of the SRA also modestly impaired PHD–H3K9me0 interaction.	RESULTS
55	60	K9me0	ptm	Pre-incubation of the SRA also modestly impaired PHD–H3K9me0 interaction.	RESULTS
32	35	SRA	structure_element	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
45	53	binds to	protein_state	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
58	61	PHD	structure_element	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
79	95	binding affinity	evidence	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
99	101	H3	protein_type	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
101	106	K9me0	ptm	These results indicate that the SRA directly binds to the PHD and inhibits its binding affinity to H3K9me0.	RESULTS
16	21	UHRF1	protein	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
39	45	closed	protein_state	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
88	98	TTD–Spacer	structure_element	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
103	110	PHD-SRA	structure_element	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
127	134	histone	protein_type	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
135	137	H3	protein_type	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
158	163	UHRF1	protein	Taken together, UHRF1 seems to adopt a closed form through intramolecular interactions (TTD–Spacer and PHD-SRA), which inhibit histone H3 tail recognition by UHRF1.	RESULTS
8	17	structure	evidence	Overall structure of TTD–Spacer	RESULTS
21	31	TTD–Spacer	structure_element	Overall structure of TTD–Spacer	RESULTS
53	58	UHRF1	protein	To investigate the intramolecular interaction within UHRF1, we first mapped the minimal regions within the Spacer for the interaction with the TTD (Supplementary Fig. 2a).	RESULTS
107	113	Spacer	structure_element	To investigate the intramolecular interaction within UHRF1, we first mapped the minimal regions within the Spacer for the interaction with the TTD (Supplementary Fig. 2a).	RESULTS
143	146	TTD	structure_element	To investigate the intramolecular interaction within UHRF1, we first mapped the minimal regions within the Spacer for the interaction with the TTD (Supplementary Fig. 2a).	RESULTS
9	18	deletions	experimental_method	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
26	32	Spacer	structure_element	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
44	58	SpacerΔ660–664	mutant	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
60	74	SpacerΔ665–669	mutant	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
76	90	SpacerΔ670–674	mutant	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
95	108	Spacer642–674	mutant	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
110	118	bound to	protein_state	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
123	126	TTD	structure_element	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
143	161	binding affinities	evidence	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
177	183	Spacer	structure_element	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
193	206	Spacer587–641	mutant	Internal deletions of the Spacer, including SpacerΔ660–664, SpacerΔ665–669, SpacerΔ670–674 and Spacer642–674, bound to the TTD with comparable binding affinities to that of the Spacer, whereas Spacer587–641 showed no detectable interaction.	RESULTS
0	14	SpacerΔ642–651	mutant	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
16	30	SpacerΔ650–654	mutant	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
35	49	SpacerΔ655–659	mutant	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
65	83	binding affinities	evidence	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
110	117	642–674	residue_range	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
136	146	TTD–Spacer	structure_element	SpacerΔ642–651, SpacerΔ650–654 and SpacerΔ655–659 also decreased binding affinities, indicating that residues 642–674 are important for TTD–Spacer interaction.	RESULTS
23	41	solution structure	evidence	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
49	52	TTD	structure_element	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
63	70	134–285	residue_range	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
72	80	bound to	protein_state	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
81	94	Spacer627–674	residue_range	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
111	114	NMR	experimental_method	We next determined the solution structure of the TTD (residues 134–285) bound to Spacer627–674 by conventional NMR techniques (Supplementary Table 3 and Supplementary Fig. 3a,b).	RESULTS
7	24	complex structure	evidence	In the complex structure, each Tudor domain adopts a ‘Royal' fold containing a characteristic five-stranded β-sheet and the two Tudor domains tightly pack against each other with a buried area of 573 Å2 (Fig. 3a).	RESULTS
31	43	Tudor domain	structure_element	In the complex structure, each Tudor domain adopts a ‘Royal' fold containing a characteristic five-stranded β-sheet and the two Tudor domains tightly pack against each other with a buried area of 573 Å2 (Fig. 3a).	RESULTS
53	65	‘Royal' fold	structure_element	In the complex structure, each Tudor domain adopts a ‘Royal' fold containing a characteristic five-stranded β-sheet and the two Tudor domains tightly pack against each other with a buried area of 573 Å2 (Fig. 3a).	RESULTS
94	115	five-stranded β-sheet	structure_element	In the complex structure, each Tudor domain adopts a ‘Royal' fold containing a characteristic five-stranded β-sheet and the two Tudor domains tightly pack against each other with a buried area of 573 Å2 (Fig. 3a).	RESULTS
128	141	Tudor domains	structure_element	In the complex structure, each Tudor domain adopts a ‘Royal' fold containing a characteristic five-stranded β-sheet and the two Tudor domains tightly pack against each other with a buried area of 573 Å2 (Fig. 3a).	RESULTS
4	7	TTD	structure_element	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
39	54	TTD–PHD–H3K9me3	complex_assembly	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
63	72	structure	evidence	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
92	118	root-mean-square deviation	evidence	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
167	173	Spacer	structure_element	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
230	233	TTD	structure_element	The TTD adopts similar fold to that in TTD–PHD–H3K9me3 complex structure (PDB: 4GY5) with a root-mean-square deviation of 1.09 Å for 128 Cα atoms, indicating that the Spacer does not result in obvious conformational change of the TTD (Fig. 3b).	RESULTS
4	10	Spacer	structure_element	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
21	28	643–655	residue_range	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
64	85	extended conformation	protein_state	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
90	98	binds to	protein_state	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
102	115	acidic groove	site	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
123	126	TTD	structure_element	The Spacer (residues 643–655 were built in the model) adopts an extended conformation and binds to an acidic groove on the TTD (Fig. 3c).	RESULTS
4	14	TTD–Spacer	structure_element	The TTD–Spacer interaction is mediated by a number of hydrogen bonds (Fig. 3d).	RESULTS
54	68	hydrogen bonds	bond_interaction	The TTD–Spacer interaction is mediated by a number of hydrogen bonds (Fig. 3d).	RESULTS
26	30	K648	residue_name_number	The side chain of residue K648 forms hydrogen bonds with the carbonyl oxygen atom of D189 and side chain of D190 of the TTD.	RESULTS
37	51	hydrogen bonds	bond_interaction	The side chain of residue K648 forms hydrogen bonds with the carbonyl oxygen atom of D189 and side chain of D190 of the TTD.	RESULTS
85	89	D189	residue_name_number	The side chain of residue K648 forms hydrogen bonds with the carbonyl oxygen atom of D189 and side chain of D190 of the TTD.	RESULTS
108	112	D190	residue_name_number	The side chain of residue K648 forms hydrogen bonds with the carbonyl oxygen atom of D189 and side chain of D190 of the TTD.	RESULTS
120	123	TTD	structure_element	The side chain of residue K648 forms hydrogen bonds with the carbonyl oxygen atom of D189 and side chain of D190 of the TTD.	RESULTS
26	30	R649	residue_name_number	The side chain of residue R649 packs against an acidic surface mainly formed by residues D142 and E153.	RESULTS
31	44	packs against	bond_interaction	The side chain of residue R649 packs against an acidic surface mainly formed by residues D142 and E153.	RESULTS
89	93	D142	residue_name_number	The side chain of residue R649 packs against an acidic surface mainly formed by residues D142 and E153.	RESULTS
98	102	E153	residue_name_number	The side chain of residue R649 packs against an acidic surface mainly formed by residues D142 and E153.	RESULTS
8	12	S651	residue_name_number	Residue S651 forms hydrogen bonds with the main chain of residues G236 and W238.	RESULTS
19	33	hydrogen bonds	bond_interaction	Residue S651 forms hydrogen bonds with the main chain of residues G236 and W238.	RESULTS
66	70	G236	residue_name_number	Residue S651 forms hydrogen bonds with the main chain of residues G236 and W238.	RESULTS
75	79	W238	residue_name_number	Residue S651 forms hydrogen bonds with the main chain of residues G236 and W238.	RESULTS
40	54	hydrogen bonds	bond_interaction	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
79	83	K650	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
85	89	A652	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
91	95	G653	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
100	104	G654	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
112	118	Spacer	structure_element	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
132	136	N228	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
138	142	G236	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
147	151	W238	residue_name_number	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
159	162	TTD	structure_element	The interaction is further supported by hydrogen bonds formed between residues K650, A652, G653 and G654 of the Spacer and residues N228, G236 and W238 of the TTD, respectively.	RESULTS
20	39	structural analyses	experimental_method	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
41	49	mutation	experimental_method	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
50	55	D142A	mutant	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
56	61	E153A	mutant	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
69	72	TTD	structure_element	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
108	114	Spacer	structure_element	In support of above structural analyses, mutation D142A/E153A of the TTD abolished its interaction with the Spacer (Fig. 3e).	RESULTS
0	9	Mutations	experimental_method	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
10	15	K648D	mutant	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
20	25	S651D	mutant	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
33	39	Spacer	structure_element	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
56	74	binding affinities	evidence	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
82	85	TTD	structure_element	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
91	99	mutation	experimental_method	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
100	105	R649A	mutant	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
113	119	Spacer	structure_element	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
171	187	binding affinity	evidence	Mutations K648D and S651D of the Spacer decreased their binding affinities to the TTD, and mutation R649A of the Spacer showed more significant decrease (∼13-fold) in the binding affinity (Fig. 3f).	RESULTS
21	30	mutations	experimental_method	As negative control, mutations S639D and S666D of the Spacer showed little effect on the interaction.	RESULTS
31	36	S639D	mutant	As negative control, mutations S639D and S666D of the Spacer showed little effect on the interaction.	RESULTS
41	46	S666D	mutant	As negative control, mutations S639D and S666D of the Spacer showed little effect on the interaction.	RESULTS
54	60	Spacer	structure_element	As negative control, mutations S639D and S666D of the Spacer showed little effect on the interaction.	RESULTS
15	30	phosphorylation	ptm	Interestingly, phosphorylation at residue S651 of UHRF1 was observed in previous mass-spectrometry analyses.	RESULTS
42	46	S651	residue_name_number	Interestingly, phosphorylation at residue S651 of UHRF1 was observed in previous mass-spectrometry analyses.	RESULTS
50	55	UHRF1	protein	Interestingly, phosphorylation at residue S651 of UHRF1 was observed in previous mass-spectrometry analyses.	RESULTS
81	98	mass-spectrometry	experimental_method	Interestingly, phosphorylation at residue S651 of UHRF1 was observed in previous mass-spectrometry analyses.	RESULTS
18	28	unmodified	protein_state	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
40	53	Spacer642–664	mutant	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
57	72	phosphorylation	ptm	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
76	80	S651	residue_name_number	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
104	120	binding affinity	evidence	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
128	131	TTD	structure_element	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
177	192	phosphorylation	ptm	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
244	249	UHRF1	protein	Compared with the unmodified peptide of Spacer642–664, a phosphorylation at S651 markedly decreased the binding affinity to the TTD (Supplementary Fig. 2b), suggesting that the phosphorylation may regulate the intramolecular interaction within UHRF1.	RESULTS
4	10	spacer	structure_element	The spacer binds to the TTD by competing with the linker	RESULTS
11	19	binds to	protein_state	The spacer binds to the TTD by competing with the linker	RESULTS
24	27	TTD	structure_element	The spacer binds to the TTD by competing with the linker	RESULTS
50	56	linker	structure_element	The spacer binds to the TTD by competing with the linker	RESULTS
35	38	TTD	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
39	47	binds to	protein_state	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
50	63	linker region	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
79	82	TTD	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
87	90	PHD	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
101	108	286–306	residue_range	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
121	127	Linker	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
143	153	TTD–Linker	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
183	185	H3	protein_type	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
185	190	K9me3	ptm	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
206	213	TTD–PHD	structure_element	Previous studies indicate that the TTD binds to a linker region connecting the TTD and PHD (residues 286–306, designated Linker, Fig. 1a), and TTD–Linker interaction is essential for H3K9me3 recognition by TTD–PHD.	RESULTS
0	10	Comparison	experimental_method	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
14	24	TTD–Spacer	structure_element	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
29	44	TTD–PHD–H3K9me3	complex_assembly	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
57	67	structures	evidence	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
87	93	Spacer	structure_element	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
102	108	Linker	structure_element	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
121	124	TTD	structure_element	Comparison of TTD–Spacer and TTD–PHD–H3K9me3 (PDB: 4GY5) structures indicates that the Spacer and the Linker bind to the TTD in a similar manner in the two complexes (Fig. 3b).	RESULTS
3	18	TTD–PHD–H3K9me3	complex_assembly	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
19	28	structure	evidence	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
39	43	R295	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
45	49	R296	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
54	58	S298	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
66	72	Linker	structure_element	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
121	125	K648	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
127	131	R649	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
136	140	S651	residue_name_number	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
148	154	Spacer	structure_element	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
158	168	TTD–Spacer	structure_element	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
169	178	structure	evidence	In TTD–PHD–H3K9me3 structure, residues R295, R296 and S298 of the Linker adopt almost identical conformation to residues K648, R649 and S651 of the Spacer in TTD–Spacer structure, respectively.	RESULTS
33	43	TTD–Linker	structure_element	Similar intramolecular contacts (TTD–Linker and TTD–Spacer) were observed in the two structures (Fig. 3b,d and Supplementary Fig. 4a).	RESULTS
48	58	TTD–Spacer	structure_element	Similar intramolecular contacts (TTD–Linker and TTD–Spacer) were observed in the two structures (Fig. 3b,d and Supplementary Fig. 4a).	RESULTS
85	95	structures	evidence	Similar intramolecular contacts (TTD–Linker and TTD–Spacer) were observed in the two structures (Fig. 3b,d and Supplementary Fig. 4a).	RESULTS
10	16	Spacer	structure_element	Thus, the Spacer may disrupt the TTD–Linker interaction and inhibits the recognition of H3K9me3 by TTD–PHD.	RESULTS
33	43	TTD–Linker	structure_element	Thus, the Spacer may disrupt the TTD–Linker interaction and inhibits the recognition of H3K9me3 by TTD–PHD.	RESULTS
88	90	H3	protein_type	Thus, the Spacer may disrupt the TTD–Linker interaction and inhibits the recognition of H3K9me3 by TTD–PHD.	RESULTS
90	95	K9me3	ptm	Thus, the Spacer may disrupt the TTD–Linker interaction and inhibits the recognition of H3K9me3 by TTD–PHD.	RESULTS
99	106	TTD–PHD	structure_element	Thus, the Spacer may disrupt the TTD–Linker interaction and inhibits the recognition of H3K9me3 by TTD–PHD.	RESULTS
85	91	Linker	structure_element	To test this hypothesis, we first investigated the potential competition between the Linker and the Spacer for their interaction with the TTD.	RESULTS
100	106	Spacer	structure_element	To test this hypothesis, we first investigated the potential competition between the Linker and the Spacer for their interaction with the TTD.	RESULTS
138	141	TTD	structure_element	To test this hypothesis, we first investigated the potential competition between the Linker and the Spacer for their interaction with the TTD.	RESULTS
4	7	ITC	experimental_method	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
34	40	Linker	structure_element	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
50	57	289–306	residue_range	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
59	67	bound to	protein_state	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
72	75	TTD	structure_element	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
83	99	binding affinity	evidence	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
169	175	Spacer	structure_element	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
185	187	KD	evidence	The ITC experiment shows that the Linker peptide (289–306) bound to the TTD with a binding affinity of 24.04 μM (Supplementary Fig. 4b), ∼15-fold lower than that of the Spacer peptide (KD=1.59 μM, Fig. 3e).	RESULTS
4	19	competitive ITC	experimental_method	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
42	69	TTD–Spacer binding affinity	evidence	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
106	117	presence of	protein_state	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
122	128	Linker	structure_element	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
138	148	TTD–Linker	structure_element	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
182	193	presence of	protein_state	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
198	204	Spacer	structure_element	The competitive ITC experiments show that TTD–Spacer binding affinity decreased by a factor of two in the presence of the Linker, whereas TTD–Linker interaction was abolished in the presence of the Spacer (Supplementary Fig. 4c).	RESULTS
14	24	TTD–Spacer	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
38	40	KD	evidence	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
51	58	TTD–PHD	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
73	89	binding affinity	evidence	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
97	103	Spacer	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
105	107	KD	evidence	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
127	135	mutation	experimental_method	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
136	141	R295D	mutant	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
142	147	R296D	mutant	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
160	166	Linker	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
185	195	TTD–Linker	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
212	219	TTD–PHD	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
249	265	binding affinity	evidence	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
267	269	KD	evidence	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
326	332	Spacer	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
341	347	Linker	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
360	372	binding site	site	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
380	383	TTD	structure_element	Compared with TTD–Spacer interaction (KD=1.48 μM), TTD–PHD decreased the binding affinity to the Spacer (KD=10.68 μM), whereas mutation R295D/R296D (within the Linker and important for TTD–Linker interaction) of TTD–PHD showed minor decrease in the binding affinity (KD=2.69 μM; Fig. 3g), indicating a competition between the Spacer and the Linker on the same binding site of the TTD.	RESULTS
22	28	Linker	structure_element	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
48	55	TTD-PHD	structure_element	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
69	79	TTD–Spacer	structure_element	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
121	127	Spacer	structure_element	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
148	155	TTD–PHD	structure_element	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
170	186	binding affinity	evidence	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
188	190	KD	evidence	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
268	273	UHRF1	protein	Notably, although the Linker (in the context of TTD-PHD) impairs the TTD–Spacer interaction to some extent, the isolated Spacer could still bind to TTD–PHD with moderate binding affinity (KD=10.68 μM), supporting the existence of the intramolecular interaction within UHRF1.	RESULTS
16	26	TTD–Spacer	structure_element	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
64	75	full-length	protein_state	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
76	81	UHRF1	protein	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
99	110	truncations	experimental_method	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
114	119	UHRF1	protein	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
127	146	GST pull-down assay	experimental_method	To test whether TTD–Spacer association exists in the context of full-length UHRF1, we used various truncations of UHRF1 in the GST pull-down assay.	RESULTS
25	36	full-length	protein_state	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
37	42	UHRF1	protein	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
47	56	UHRF1ΔSRA	mutant	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
84	94	GST-tagged	protein_state	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
95	98	TTD	structure_element	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
100	106	Linker	structure_element	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
110	116	Spacer	structure_element	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
134	144	TTD–Spacer	structure_element	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
157	163	in-cis	protein_state	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
171	182	full-length	protein_state	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
183	188	UHRF1	protein	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
192	201	UHRF1ΔSRA	mutant	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
212	222	TTD–Spacer	structure_element	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
241	249	in-trans	protein_state	As indicated in Fig. 3h, full-length UHRF1 and UHRF1ΔSRA showed no interaction with GST-tagged TTD, Linker or Spacer, suggesting that TTD–Spacer interaction in-cis within full-length UHRF1 or UHRF1ΔSRA prohibits TTD–Spacer complex formation in-trans.	RESULTS
13	22	UHRF1ΔTTD	mutant	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
23	31	bound to	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
32	35	GST	experimental_method	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
36	39	TTD	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
45	58	UHRF1Δ627–674	mutant	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
59	67	bound to	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
68	71	GST	experimental_method	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
72	78	Spacer	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
104	114	TTD–Spacer	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
127	133	in-cis	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
135	145	TTD–Spacer	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
165	173	in-trans	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
195	198	TTD	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
199	207	binds to	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
212	218	Spacer	structure_element	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
237	248	full-length	protein_state	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
249	254	UHRF1	protein	In contrast, UHRF1ΔTTD bound to GST-TTD, and UHRF1Δ627–674 bound to GST-Spacer, indicating that lack of TTD–Spacer interaction in-cis, TTD–Spacer complex could form in-trans, supporting that the TTD binds to the Spacer in the context of full-length UHRF1.	RESULTS
10	13	GST	experimental_method	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
14	20	Linker	structure_element	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
75	84	wild-type	protein_state	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
101	106	UHRF1	protein	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
124	134	TTD–Linker	structure_element	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
175	185	TTD–Spacer	structure_element	Moreover, GST-Linker showed very weak if not undetectable interaction with wild-type or deletions of UHRF1, suggesting that TTD–Linker interaction is much weaker than that of TTD–Spacer.	RESULTS
16	21	UHRF1	protein	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
31	37	closed	protein_state	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
65	71	Spacer	structure_element	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
72	80	binds to	protein_state	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
85	88	TTD	structure_element	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
116	122	Linker	structure_element	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
147	149	H3	protein_type	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
149	154	K9me3	ptm	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
170	175	UHRF1	protein	Taken together, UHRF1 adopts a closed conformation, in which the Spacer binds to the TTD through competing with the Linker, and therefore inhibits H3K9me3 recognition by UHRF1.	RESULTS
4	10	spacer	structure_element	The spacer inhibits H3K9me3 recognition by the isolated TTD	RESULTS
20	22	H3	protein_type	The spacer inhibits H3K9me3 recognition by the isolated TTD	RESULTS
22	27	K9me3	ptm	The spacer inhibits H3K9me3 recognition by the isolated TTD	RESULTS
56	59	TTD	structure_element	The spacer inhibits H3K9me3 recognition by the isolated TTD	RESULTS
34	36	H3	protein_type	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
36	41	K9me3	ptm	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
42	50	binds to	protein_state	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
55	58	TTD	structure_element	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
82	97	TTD–PHD–H3K9me3	complex_assembly	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
109	120	TTD-H3K9me3	complex_assembly	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
133	143	structures	evidence	Our previous study indicates that H3K9me3 binds to the TTD in different manner in TTD–PHD–H3K9me3 (ref.) and TTD-H3K9me3 (PDB: 2L3R) structures.	RESULTS
12	15	TTD	structure_element	Because the TTD is always associated with the PHD, whether the pattern of TTD–H3K9me3 interaction exists in vivo remains unknown.	RESULTS
46	49	PHD	structure_element	Because the TTD is always associated with the PHD, whether the pattern of TTD–H3K9me3 interaction exists in vivo remains unknown.	RESULTS
74	85	TTD–H3K9me3	complex_assembly	Because the TTD is always associated with the PHD, whether the pattern of TTD–H3K9me3 interaction exists in vivo remains unknown.	RESULTS
14	24	comparison	experimental_method	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
28	39	TTD–H3K9me3	complex_assembly	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
44	54	TTD–Spacer	structure_element	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
55	65	structures	evidence	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
81	83	H3	protein_type	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
83	88	K9me3	ptm	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
97	103	Spacer	structure_element	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
134	137	TTD	structure_element	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
183	189	Spacer	structure_element	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
206	208	H3	protein_type	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
208	213	K9me3	ptm	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
242	245	TTD	structure_element	Nevertheless, comparison of TTD–H3K9me3 and TTD–Spacer structures indicates that H3K9me3 and the Spacer overlap on the surface of the TTD (Supplementary Fig. 4d), suggesting that the Spacer might block the H3K9me3 recognition by the isolated TTD.	RESULTS
39	45	Spacer	structure_element	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
56	67	TTD–H3K9me3	complex_assembly	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
93	114	TTD-binding defective	protein_state	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
115	122	mutants	protein_state	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
130	136	Spacer	structure_element	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
144	147	SRA	structure_element	As shown in Supplementary Fig. 4e, the Spacer inhibited TTD–H3K9me3 interaction, whereas its TTD-binding defective mutants of the Spacer or the SRA (a negative control) markedly decreased the inhibition.	RESULTS
69	80	full-length	protein_state	We next tested whether such inhibition also occurs in the context of full-length UHRF1.	RESULTS
81	86	UHRF1	protein	We next tested whether such inhibition also occurs in the context of full-length UHRF1.	RESULTS
14	25	full-length	protein_state	Compared with full-length UHRF1, UHRF1Δ627–674 enhanced H3K9me3-binding affinity by a factor of four (Supplementary Fig. 4f).	RESULTS
26	31	UHRF1	protein	Compared with full-length UHRF1, UHRF1Δ627–674 enhanced H3K9me3-binding affinity by a factor of four (Supplementary Fig. 4f).	RESULTS
33	46	UHRF1Δ627–674	mutant	Compared with full-length UHRF1, UHRF1Δ627–674 enhanced H3K9me3-binding affinity by a factor of four (Supplementary Fig. 4f).	RESULTS
56	80	H3K9me3-binding affinity	evidence	Compared with full-length UHRF1, UHRF1Δ627–674 enhanced H3K9me3-binding affinity by a factor of four (Supplementary Fig. 4f).	RESULTS
19	43	H3K9me3-binding affinity	evidence	The restoration of H3K9me3-binding affinity is not dramatic because the PHD still binds to histone H3 in both proteins.	RESULTS
72	75	PHD	structure_element	The restoration of H3K9me3-binding affinity is not dramatic because the PHD still binds to histone H3 in both proteins.	RESULTS
82	90	binds to	protein_state	The restoration of H3K9me3-binding affinity is not dramatic because the PHD still binds to histone H3 in both proteins.	RESULTS
91	98	histone	protein_type	The restoration of H3K9me3-binding affinity is not dramatic because the PHD still binds to histone H3 in both proteins.	RESULTS
99	101	H3	protein_type	The restoration of H3K9me3-binding affinity is not dramatic because the PHD still binds to histone H3 in both proteins.	RESULTS
53	63	UHRF1D334A	mutant	To exclude this effect, we performed the assay using UHRF1D334A, which abolishes H3R2-binding affinity of the PHD.	RESULTS
71	80	abolishes	protein_state	To exclude this effect, we performed the assay using UHRF1D334A, which abolishes H3R2-binding affinity of the PHD.	RESULTS
81	102	H3R2-binding affinity	evidence	To exclude this effect, we performed the assay using UHRF1D334A, which abolishes H3R2-binding affinity of the PHD.	RESULTS
110	113	PHD	structure_element	To exclude this effect, we performed the assay using UHRF1D334A, which abolishes H3R2-binding affinity of the PHD.	RESULTS
0	10	UHRF1D334A	mutant	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
31	55	H3K9me3-binding affinity	evidence	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
65	75	UHRF1D334A	mutant	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
76	84	Δ627–674	mutant	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
111	135	H3K9me3-binding affinity	evidence	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
137	139	KD	evidence	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
189	191	H3	protein_type	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
191	196	K9me3	ptm	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
216	219	TTD	structure_element	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
238	244	Spacer	structure_element	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
286	289	TTD	structure_element	UHRF1D334A showed undetectable H3K9me3-binding affinity, whereas UHRF1D334A&Δ627–674 dramatically restored its H3K9me3-binding affinity (KD=8.69 μM; Supplementary Fig. 4f), indicating that H3K9me3 recognition by the TTD is blocked by the Spacer through competitive interaction with the TTD.	RESULTS
14	19	R295D	mutant	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
20	25	R296D	mutant	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
26	32	mutant	protein_state	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
36	47	full-length	protein_state	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
48	53	UHRF1	protein	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
71	87	binding affinity	evidence	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
91	93	H3	protein_type	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
93	98	K9me3	ptm	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
121	130	wild type	protein_state	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
149	157	mutation	experimental_method	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
161	166	R295D	mutant	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
167	172	R296D	mutant	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
181	191	TTD–Spacer	structure_element	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
227	232	UHRF1	protein	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
258	264	closed	protein_state	Moreover, the R295D/R296D mutant of full-length UHRF1 showed decreased binding affinity to H3K9me3 (eightfold lower than wild type), suggesting that mutation of R295D/R296D favours TTD–Spacer interaction and therefore promotes UHRF1 to exhibit a more stable closed conformation (Supplementary Fig. 4g).	RESULTS
20	26	Spacer	structure_element	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
27	35	binds to	protein_state	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
40	43	TTD	structure_element	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
57	59	H3	protein_type	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
59	64	K9me3	ptm	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
80	85	UHRF1	protein	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
109	119	TTD–Linker	structure_element	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
156	158	H3	protein_type	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
158	163	K9me3	ptm	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
179	186	TTD–PHD	structure_element	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
205	207	H3	protein_type	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
207	212	K9me3	ptm	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
237	240	TTD	structure_element	Taken together, the Spacer binds to the TTD and inhibits H3K9me3 recognition by UHRF1 through (i) disrupting TTD–Linker interaction, which is essential for H3K9me3 recognition by TTD–PHD, (ii) prohibiting H3K9me3 binding to the isolated TTD.	RESULTS
0	15	TTD–PHD–H3K9me3	complex_assembly	TTD–PHD–H3K9me3 complex inhibits TTD–spacer interaction	RESULTS
33	43	TTD–spacer	structure_element	TTD–PHD–H3K9me3 complex inhibits TTD–spacer interaction	RESULTS
15	29	pre-incubation	experimental_method	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
33	35	H3	protein_type	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
35	40	K9me3	ptm	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
96	102	Spacer	structure_element	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
111	114	TTD	structure_element	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
115	120	alone	protein_state	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
124	131	TTD–PHD	structure_element	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
169	180	presence of	protein_state	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
185	191	Spacer	structure_element	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
235	242	TTD–PHD	structure_element	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
247	249	H3	protein_type	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
249	254	K9me3	ptm	Interestingly, pre-incubation of H3K9me3 peptide completely blocked the interaction between the Spacer and the TTD alone or TTD–PHD (Supplementary Fig. 4h), whereas the presence of the Spacer partially impaired the interaction between TTD–PHD and H3K9me3 (Fig. 2c).	RESULTS
91	98	TTD–PHD	structure_element	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
107	113	Spacer	structure_element	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
130	132	KD	evidence	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
170	177	TTD–PHD	structure_element	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
182	184	H3	protein_type	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
184	189	K9me3	ptm	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
191	193	KD	evidence	The results are also consistent with the previous observation that the interaction between TTD–PHD and the Spacer is much weaker (KD=10.68 μM, Fig. 3g) than that between TTD–PHD and H3K9me3 (KD=0.15 μM, Fig. 1d).	RESULTS
32	39	TTD–PHD	structure_element	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
40	48	binds to	protein_state	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
49	51	H3	protein_type	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
51	56	K9me3	ptm	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
58	63	UHRF1	protein	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
82	84	H3	protein_type	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
84	89	K9me3	ptm	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
98	104	Spacer	structure_element	These results suggest that once TTD–PHD binds to H3K9me3, UHRF1 will be locked by H3K9me3 and the Spacer is unlikely to fold back for the intramolecular interaction.	RESULTS
0	6	Hm-DNA	chemical	Hm-DNA disrupts intramolecular interaction within UHRF1	RESULTS
50	55	UHRF1	protein	Hm-DNA disrupts intramolecular interaction within UHRF1	RESULTS
23	29	hm-DNA	chemical	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
36	40	open	protein_state	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
45	51	closed	protein_state	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
68	73	UHRF1	protein	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
130	135	UHRF1	protein	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
136	147	truncations	experimental_method	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
155	163	presence	protein_state	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
167	177	absence of	protein_state	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
178	184	hm-DNA	chemical	To investigate whether hm-DNA could open the closed conformation of UHRF1, we first measured the intramolecular interaction using UHRF1 truncations in the presence or absence of hm-DNA.	RESULTS
4	24	GST pull-down assays	experimental_method	The GST pull-down assays show that the PHD bound to the SRA and such interaction was impaired by the addition of hm-DNA (Fig. 4a).	RESULTS
39	42	PHD	structure_element	The GST pull-down assays show that the PHD bound to the SRA and such interaction was impaired by the addition of hm-DNA (Fig. 4a).	RESULTS
43	51	bound to	protein_state	The GST pull-down assays show that the PHD bound to the SRA and such interaction was impaired by the addition of hm-DNA (Fig. 4a).	RESULTS
56	59	SRA	structure_element	The GST pull-down assays show that the PHD bound to the SRA and such interaction was impaired by the addition of hm-DNA (Fig. 4a).	RESULTS
113	119	hm-DNA	chemical	The GST pull-down assays show that the PHD bound to the SRA and such interaction was impaired by the addition of hm-DNA (Fig. 4a).	RESULTS
0	27	H3 peptide pull-down assays	experimental_method	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
38	44	hm-DNA	chemical	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
63	89	H3K9me0-binding affinities	evidence	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
93	98	UHRF1	protein	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
99	110	truncations	experimental_method	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
122	129	PHD-SRA	structure_element	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
139	146	PHD-SRA	structure_element	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
148	159	TTD-PHD-SRA	structure_element	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
161	179	TTD-PHD-SRA-Spacer	structure_element	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
181	190	UHRF1ΔTTD	mutant	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
195	207	UHRF1ΔSpacer	mutant	H3 peptide pull-down assays show that hm-DNA only enhanced the H3K9me0-binding affinities of UHRF1 truncations containing PHD-SRA, such as PHD-SRA, TTD-PHD-SRA, TTD-PHD-SRA-Spacer, UHRF1ΔTTD and UHRF1ΔSpacer (Fig. 4b).	RESULTS
26	32	hm-DNA	chemical	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
42	49	PHD–SRA	structure_element	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
78	102	H3K9me0-binding affinity	evidence	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
110	113	PHD	structure_element	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
145	148	TTD	structure_element	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
156	162	Spacer	structure_element	The result indicates that hm-DNA disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
14	17	TTD	structure_element	Moreover, the TTD or TTD–PHD bound to SRA–Spacer and the interaction was impaired by the addition of hm-DNA (Fig. 4c).	RESULTS
21	28	TTD–PHD	structure_element	Moreover, the TTD or TTD–PHD bound to SRA–Spacer and the interaction was impaired by the addition of hm-DNA (Fig. 4c).	RESULTS
29	37	bound to	protein_state	Moreover, the TTD or TTD–PHD bound to SRA–Spacer and the interaction was impaired by the addition of hm-DNA (Fig. 4c).	RESULTS
38	48	SRA–Spacer	structure_element	Moreover, the TTD or TTD–PHD bound to SRA–Spacer and the interaction was impaired by the addition of hm-DNA (Fig. 4c).	RESULTS
101	107	hm-DNA	chemical	Moreover, the TTD or TTD–PHD bound to SRA–Spacer and the interaction was impaired by the addition of hm-DNA (Fig. 4c).	RESULTS
4	7	ITC	experimental_method	The ITC measurements show that the presence of hm-DNA markedly impaired the interaction between the TTD and SRA–Spacer (Supplementary Fig. 5a).	RESULTS
35	46	presence of	protein_state	The ITC measurements show that the presence of hm-DNA markedly impaired the interaction between the TTD and SRA–Spacer (Supplementary Fig. 5a).	RESULTS
47	53	hm-DNA	chemical	The ITC measurements show that the presence of hm-DNA markedly impaired the interaction between the TTD and SRA–Spacer (Supplementary Fig. 5a).	RESULTS
100	103	TTD	structure_element	The ITC measurements show that the presence of hm-DNA markedly impaired the interaction between the TTD and SRA–Spacer (Supplementary Fig. 5a).	RESULTS
108	118	SRA–Spacer	structure_element	The ITC measurements show that the presence of hm-DNA markedly impaired the interaction between the TTD and SRA–Spacer (Supplementary Fig. 5a).	RESULTS
13	23	TTD–Spacer	structure_element	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
60	71	presence of	protein_state	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
76	82	hm-DNA	chemical	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
100	106	hm-DNA	chemical	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
121	127	Spacer	structure_element	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
137	140	TTD	structure_element	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
146	149	SRA	structure_element	However, the TTD–Spacer interaction was not affected by the presence of the hm-DNA, indicating that hm-DNA displaces the Spacer from the TTD in a SRA-dependent manner (Supplementary Fig. 5b).	RESULTS
23	29	hm-DNA	chemical	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
39	49	TTD–Spacer	structure_element	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
80	91	full-length	protein_state	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
92	97	UHRF1	protein	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
142	147	UHRF1	protein	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
158	182	histone-binding affinity	evidence	To investigate whether hm-DNA disrupts TTD–Spacer interaction in the context of full-length UHRF1, we monitored the conformational changes of UHRF1 using its histone-binding affinity as read-out.	RESULTS
0	10	UHRF1D334A	mutant	UHRF1D334A was used to exclude the effect of H3K9me0 recognition by the PHD.	RESULTS
45	47	H3	protein_type	UHRF1D334A was used to exclude the effect of H3K9me0 recognition by the PHD.	RESULTS
47	52	K9me0	ptm	UHRF1D334A was used to exclude the effect of H3K9me0 recognition by the PHD.	RESULTS
72	75	PHD	structure_element	UHRF1D334A was used to exclude the effect of H3K9me0 recognition by the PHD.	RESULTS
17	22	D334A	mutant	As expected, all D334A-containing mutants showed undetectable interaction with H3K9me0 (Fig. 4d).	RESULTS
34	41	mutants	protein_state	As expected, all D334A-containing mutants showed undetectable interaction with H3K9me0 (Fig. 4d).	RESULTS
79	81	H3	protein_type	As expected, all D334A-containing mutants showed undetectable interaction with H3K9me0 (Fig. 4d).	RESULTS
81	86	K9me0	ptm	As expected, all D334A-containing mutants showed undetectable interaction with H3K9me0 (Fig. 4d).	RESULTS
0	10	UHRF1D334A	mutant	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
11	19	bound to	protein_state	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
20	22	H3	protein_type	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
22	27	K9me3	ptm	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
43	54	presence of	protein_state	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
55	61	hm-DNA	chemical	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
96	106	absence of	protein_state	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
107	113	hm-DNA	chemical	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
144	147	ITC	experimental_method	UHRF1D334A bound to H3K9me3 peptide in the presence of hm-DNA, but showed no interaction in the absence of hm-DNA, which is consistent with the ITC experiments (Supplementary Fig. 4f).	RESULTS
13	23	UHRF1D334A	mutant	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
24	32	Δ627–674	mutant	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
42	50	bound to	protein_state	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
51	53	H3	protein_type	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
53	58	K9me3	ptm	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
71	81	absence of	protein_state	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
82	88	hm-DNA	chemical	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
120	128	deletion	experimental_method	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
136	142	Spacer	structure_element	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
170	177	TTD–PHD	structure_element	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
182	184	H3	protein_type	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
184	189	K9me3	ptm	In contrast, UHRF1D334A&Δ627–674 strongly bound to H3K9me3 even in the absence of hm-DNA (Fig. 4d), indicating that the deletion of the Spacer releases otherwise blocked TTD–PHD for H3K9me3 recognition.	RESULTS
52	58	Spacer	structure_element	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
59	67	binds to	protein_state	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
72	75	TTD	structure_element	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
94	105	full-length	protein_state	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
106	111	UHRF1	protein	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
165	171	hm-DNA	chemical	The results further support the conclusion that the Spacer binds to the TTD in the context of full-length UHRF1 and the intramolecular interactions are disrupted by hm-DNA.	RESULTS
26	49	peptide pull-down assay	experimental_method	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
60	67	mutants	protein_state	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
69	74	N228C	mutant	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
75	80	G653C	mutant	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
85	90	R235C	mutant	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
91	96	G654C	mutant	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
111	121	UHRF1D334A	mutant	We next performed similar peptide pull-down assay using two mutants (N228C/G653C and R235C/G654C) generated on UHRF1D334A.	RESULTS
9	13	N228	residue_name_number	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
14	18	R235	residue_name_number	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
28	31	TTD	structure_element	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
36	40	G653	residue_name_number	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
41	45	G654	residue_name_number	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
55	61	Spacer	structure_element	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
91	101	TTD–Spacer	structure_element	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
110	119	structure	evidence	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
165	173	Cysteine	residue_name	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
197	200	TTD	structure_element	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
218	224	Spacer	structure_element	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
278	293	disulphide bond	ptm	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
301	311	absence of	protein_state	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
330	344	dithiothreitol	chemical	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
346	349	DTT	chemical	Residues N228/R235 from the TTD and G653/G654 from the Spacer were chosen according to the TTD–Spacer complex structure (Supplementary Fig. 5c) so that the replaced Cysteine residues (one from the TTD and one from the Spacer) are physically close enough to each other to form a disulphide bond in the absence of reducing reagent (dithiothreitol, DTT).	RESULTS
21	27	hm-DNA	chemical	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
49	75	H3K9me3-binding affinities	evidence	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
84	91	mutants	protein_state	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
99	110	presence of	protein_state	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
111	114	DTT	chemical	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
131	141	absence of	protein_state	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
142	145	DTT	chemical	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
167	182	disulphide bond	ptm	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
201	211	absence of	protein_state	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
212	215	DTT	chemical	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
227	233	hm-DNA	chemical	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
245	255	TTD–Spacer	structure_element	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
272	274	H3	protein_type	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
274	279	K9me3	ptm	As shown in Fig. 4d, hm-DNA largely enhanced the H3K9me3-binding affinities of both mutants in the presence of DTT, but not in the absence of DTT, indicating that the disulphide bond formation (in the absence of DTT) disallows hm-DNA to disrupt TTD–Spacer interaction for H3K9me3 recognition.	RESULTS
22	24	H3	protein_type	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
24	29	K9me3	ptm	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
45	55	UHRF1D334A	mutant	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
59	69	UHRF1D334A	mutant	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
70	78	Δ627–674	mutant	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
98	101	DTT	chemical	As negative controls, H3K9me3 recognition by UHRF1D334A or UHRF1D334A&Δ627–674 is not affected by DTT.	RESULTS
52	63	full-length	protein_state	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
64	69	UHRF1	protein	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
79	85	closed	protein_state	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
105	111	Spacer	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
112	120	binds to	protein_state	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
125	128	TTD	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
133	135	H3	protein_type	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
135	140	K9me3	ptm	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
172	178	hm-DNA	chemical	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
193	199	Spacer	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
209	212	TTD	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
231	242	full-length	protein_state	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
243	248	UHRF1	protein	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
284	291	histone	protein_type	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
292	294	H3	protein_type	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
294	299	K9me3	ptm	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
348	351	PHD	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
353	356	SRA	structure_element	The above results collectively demonstrate that (i) full-length UHRF1 adopts a closed form, in which the Spacer binds to the TTD and H3K9me3 recognition is inhibited; (ii) hm-DNA displaces the Spacer from the TTD in the context of full-length UHRF1 and therefore largely enhances its histone H3K9me3-binding activity in a manner independent on the PHD (SRA is required).	RESULTS
37	43	hm-DNA	chemical	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
58	65	PHD–SRA	structure_element	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
94	118	H3K9me0-binding affinity	evidence	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
126	129	PHD	structure_element	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
161	164	TTD	structure_element	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
172	178	Spacer	structure_element	We have previously demonstrated that hm-DNA also disrupts PHD–SRA interaction and facilitates H3K9me0-binding affinity of the PHD in a manner independent on the TTD or the Spacer.	RESULTS
16	22	hm-DNA	chemical	Taken together, hm-DNA disrupts the intramolecular interactions within UHRF1, and therefore facilitates the coordinate recognition of H3K9me3 by TTD–PHD.	RESULTS
71	76	UHRF1	protein	Taken together, hm-DNA disrupts the intramolecular interactions within UHRF1, and therefore facilitates the coordinate recognition of H3K9me3 by TTD–PHD.	RESULTS
134	136	H3	protein_type	Taken together, hm-DNA disrupts the intramolecular interactions within UHRF1, and therefore facilitates the coordinate recognition of H3K9me3 by TTD–PHD.	RESULTS
136	141	K9me3	ptm	Taken together, hm-DNA disrupts the intramolecular interactions within UHRF1, and therefore facilitates the coordinate recognition of H3K9me3 by TTD–PHD.	RESULTS
145	152	TTD–PHD	structure_element	Taken together, hm-DNA disrupts the intramolecular interactions within UHRF1, and therefore facilitates the coordinate recognition of H3K9me3 by TTD–PHD.	RESULTS
4	10	spacer	structure_element	The spacer enhances hm-DNA-binding affinity of the SRA	RESULTS
20	43	hm-DNA-binding affinity	evidence	The spacer enhances hm-DNA-binding affinity of the SRA	RESULTS
51	54	SRA	structure_element	The spacer enhances hm-DNA-binding affinity of the SRA	RESULTS
19	25	hm-DNA	chemical	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
34	44	TTD–Spacer	structure_element	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
80	86	Spacer	structure_element	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
102	108	hm-DNA	chemical	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
128	131	SRA	structure_element	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
168	174	hm-DNA	chemical	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
194	199	UHRF1	protein	To investigate how hm-DNA impairs TTD–Spacer interaction, we tested whether the Spacer is involved in hm-DNA recognition by the SRA, which is the only known domain for hm-DNA recognition within UHRF1.	RESULTS
7	43	electrophoretic mobility-shift assay	experimental_method	In the electrophoretic mobility-shift assay, SRA–Spacer showed higher hm-DNA-binding affinity than the SRA alone (Supplementary Fig. 6a).	RESULTS
45	55	SRA–Spacer	structure_element	In the electrophoretic mobility-shift assay, SRA–Spacer showed higher hm-DNA-binding affinity than the SRA alone (Supplementary Fig. 6a).	RESULTS
70	93	hm-DNA-binding affinity	evidence	In the electrophoretic mobility-shift assay, SRA–Spacer showed higher hm-DNA-binding affinity than the SRA alone (Supplementary Fig. 6a).	RESULTS
103	106	SRA	structure_element	In the electrophoretic mobility-shift assay, SRA–Spacer showed higher hm-DNA-binding affinity than the SRA alone (Supplementary Fig. 6a).	RESULTS
107	112	alone	protein_state	In the electrophoretic mobility-shift assay, SRA–Spacer showed higher hm-DNA-binding affinity than the SRA alone (Supplementary Fig. 6a).	RESULTS
0	3	ITC	experimental_method	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
27	37	SRA–Spacer	structure_element	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
38	46	bound to	protein_state	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
47	53	hm-DNA	chemical	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
73	89	binding affinity	evidence	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
91	93	KD	evidence	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
112	115	SRA	structure_element	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
117	119	KD	evidence	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
143	149	Spacer	structure_element	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
150	155	alone	protein_state	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
183	189	hm-DNA	chemical	ITC measurements show that SRA–Spacer bound to hm-DNA with a much higher binding affinity (KD=1.75 μM) than the SRA (KD=25.12 μM), whereas the Spacer alone showed no interaction with hm-DNA (Fig. 5a).	RESULTS
7	36	fluorescence polarization (FP	experimental_method	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
52	62	SRA–Spacer	structure_element	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
64	75	full-length	protein_state	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
76	81	UHRF1	protein	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
86	95	UHRF1ΔTTD	mutant	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
114	139	hm-DNA-binding affinities	evidence	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
193	198	UHRF1	protein	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
199	207	binds to	protein_state	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
208	214	hm-DNA	chemical	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
225	230	UHRF1	protein	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
240	246	closed	protein_state	In the fluorescence polarization (FP) measurements, SRA–Spacer, full-length UHRF1 and UHRF1ΔTTD showed comparable hm-DNA-binding affinities (Fig. 5b and Supplementary Table 4), suggesting that UHRF1 binds to hm-DNA no matter UHRF1 adopts a closed form or not.	RESULTS
13	22	UHRF1ΔSRA	mutant	In contrast, UHRF1ΔSRA abolished hm-DNA-binding affinity, indicating that the SRA is essential for hm-DNA recognition.	RESULTS
33	56	hm-DNA-binding affinity	evidence	In contrast, UHRF1ΔSRA abolished hm-DNA-binding affinity, indicating that the SRA is essential for hm-DNA recognition.	RESULTS
78	81	SRA	structure_element	In contrast, UHRF1ΔSRA abolished hm-DNA-binding affinity, indicating that the SRA is essential for hm-DNA recognition.	RESULTS
99	105	hm-DNA	chemical	In contrast, UHRF1ΔSRA abolished hm-DNA-binding affinity, indicating that the SRA is essential for hm-DNA recognition.	RESULTS
14	25	full-length	protein_state	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
26	31	UHRF1	protein	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
33	46	UHRF1Δ627–674	mutant	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
61	84	hm-DNA-binding affinity	evidence	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
142	148	Spacer	structure_element	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
176	182	hm-DNA	chemical	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
213	224	full-length	protein_state	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
225	230	UHRF1	protein	Compared with full-length UHRF1, UHRF1Δ627–674 decreased the hm-DNA-binding affinity by a factor of 14 (Fig. 5b), further supporting that the Spacer plays an important role in hm-DNA recognition in the context of full-length UHRF1.	RESULTS
13	38	hm-DNA-binding affinities	evidence	In addition, hm-DNA-binding affinities of SRA or SRA–Spacer did not obviously vary upon the change of DNA lengths but did decrease with the increasing salt concentrations (Supplementary Fig. 6b,c and Supplementary Table 5).	RESULTS
42	45	SRA	structure_element	In addition, hm-DNA-binding affinities of SRA or SRA–Spacer did not obviously vary upon the change of DNA lengths but did decrease with the increasing salt concentrations (Supplementary Fig. 6b,c and Supplementary Table 5).	RESULTS
49	59	SRA–Spacer	structure_element	In addition, hm-DNA-binding affinities of SRA or SRA–Spacer did not obviously vary upon the change of DNA lengths but did decrease with the increasing salt concentrations (Supplementary Fig. 6b,c and Supplementary Table 5).	RESULTS
32	38	Spacer	structure_element	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
48	56	binds to	protein_state	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
61	64	TTD	structure_element	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
78	80	H3	protein_type	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
80	85	K9me3	ptm	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
103	108	UHRF1	protein	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
116	122	closed	protein_state	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
158	164	hm-DNA	chemical	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
184	187	SRA	structure_element	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
193	198	UHRF1	protein	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
199	207	binds to	protein_state	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
208	214	hm-DNA	chemical	These results indicate that the Spacer not only binds to the TTD and inhibits H3K9me3 recognition when UHRF1 adopts closed conformation, but also facilitates hm-DNA recognition by the SRA when UHRF1 binds to hm-DNA.	RESULTS
41	47	Spacer	structure_element	We next mapped the minimal region of the Spacer for the enhancement of hm-DNA-binding affinity.	RESULTS
71	94	hm-DNA-binding affinity	evidence	We next mapped the minimal region of the Spacer for the enhancement of hm-DNA-binding affinity.	RESULTS
0	14	SRA–Spacer-661	mutant	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
25	32	414–661	residue_range	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
58	81	hm-DNA-binding affinity	evidence	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
104	114	SRA–Spacer	structure_element	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
125	132	414–674	residue_range	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
143	157	SRA–Spacer-652	mutant	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
162	176	SRA–Spacer-642	mutant	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
202	227	hm-DNA-binding affinities	evidence	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
264	271	642–661	residue_range	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
300	323	hm-DNA-binding affinity	evidence	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
331	334	SRA	structure_element	SRA–Spacer-661 (residues 414–661) still maintained strong hm-DNA-binding affinity comparable to that of SRA–Spacer (residues 414–674), whereas SRA–Spacer-652 and SRA–Spacer-642 markedly decreased their hm-DNA-binding affinities (Fig. 5c), indicating that residues 642–661 are important for enhancing hm-DNA-binding affinity of the SRA.	RESULTS
46	52	Spacer	structure_element	This minimal region largely overlaps with the Spacer region (643–655) essential for TTD interaction.	RESULTS
61	68	643–655	residue_range	This minimal region largely overlaps with the Spacer region (643–655) essential for TTD interaction.	RESULTS
84	87	TTD	structure_element	This minimal region largely overlaps with the Spacer region (643–655) essential for TTD interaction.	RESULTS
23	40	crystal structure	evidence	We also determined the crystal structure of SRA–Spacer bound to hm-DNA at 3.15 Å resolution (Supplementary Table 6 and Supplementary Fig. 7a).	RESULTS
44	54	SRA–Spacer	structure_element	We also determined the crystal structure of SRA–Spacer bound to hm-DNA at 3.15 Å resolution (Supplementary Table 6 and Supplementary Fig. 7a).	RESULTS
55	63	bound to	protein_state	We also determined the crystal structure of SRA–Spacer bound to hm-DNA at 3.15 Å resolution (Supplementary Table 6 and Supplementary Fig. 7a).	RESULTS
64	70	hm-DNA	chemical	We also determined the crystal structure of SRA–Spacer bound to hm-DNA at 3.15 Å resolution (Supplementary Table 6 and Supplementary Fig. 7a).	RESULTS
4	13	structure	evidence	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
29	32	SRA	structure_element	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
33	41	binds to	protein_state	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
42	48	hm-DNA	chemical	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
113	123	SRA-hm-DNA	complex_assembly	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
124	134	structures	evidence	The structure shows that the SRA binds to hm-DNA in a manner similar to that observed in the previously reported SRA-hm-DNA structures.	RESULTS
17	33	electron density	evidence	Intriguingly, no electron density was observed for the Spacer.	RESULTS
55	61	Spacer	structure_element	Intriguingly, no electron density was observed for the Spacer.	RESULTS
35	41	Spacer	structure_element	A possible explanation is that the Spacer facilitates SRA–hm-DNA interaction through nonspecific salt bridge contacts because DNA is rich in acidic groups and the Spacer is rich in basic residues (Supplementary Fig. 7b).	RESULTS
54	64	SRA–hm-DNA	complex_assembly	A possible explanation is that the Spacer facilitates SRA–hm-DNA interaction through nonspecific salt bridge contacts because DNA is rich in acidic groups and the Spacer is rich in basic residues (Supplementary Fig. 7b).	RESULTS
97	108	salt bridge	bond_interaction	A possible explanation is that the Spacer facilitates SRA–hm-DNA interaction through nonspecific salt bridge contacts because DNA is rich in acidic groups and the Spacer is rich in basic residues (Supplementary Fig. 7b).	RESULTS
126	129	DNA	chemical	A possible explanation is that the Spacer facilitates SRA–hm-DNA interaction through nonspecific salt bridge contacts because DNA is rich in acidic groups and the Spacer is rich in basic residues (Supplementary Fig. 7b).	RESULTS
163	169	Spacer	structure_element	A possible explanation is that the Spacer facilitates SRA–hm-DNA interaction through nonspecific salt bridge contacts because DNA is rich in acidic groups and the Spacer is rich in basic residues (Supplementary Fig. 7b).	RESULTS
77	82	UHRF1	protein	The nonspecific interaction is consistent with the previous observation that UHRF1 has no DNA sequence selectivity besides hm-CpG dinucleotide.	RESULTS
90	93	DNA	chemical	The nonspecific interaction is consistent with the previous observation that UHRF1 has no DNA sequence selectivity besides hm-CpG dinucleotide.	RESULTS
123	142	hm-CpG dinucleotide	chemical	The nonspecific interaction is consistent with the previous observation that UHRF1 has no DNA sequence selectivity besides hm-CpG dinucleotide.	RESULTS
4	10	spacer	structure_element	The spacer is important for PCH localization of UHRF1	RESULTS
48	53	UHRF1	protein	The spacer is important for PCH localization of UHRF1	RESULTS
31	37	Spacer	structure_element	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
59	64	UHRF1	protein	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
78	103	transiently overexpressed	experimental_method	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
104	114	GFP-tagged	protein_state	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
115	124	wild type	protein_state	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
128	135	mutants	protein_state	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
139	144	UHRF1	protein	To investigate the role of the Spacer in the regulation of UHRF1 function, we transiently overexpressed GFP-tagged wild type or mutants of UHRF1 in NIH3T3 cells to determine their subcellular localization.	RESULTS
32	41	wild-type	protein_state	For the NIH3T3 cells expressing wild-type UHRF1, most cells (∼74.6%) showed a focal pattern of protein that is co-localized with 4,6-diamidino-2-phenylindole (DAPI) foci (Fig. 5d), whereas the rest cells showed a diffuse nuclear staining pattern.	RESULTS
42	47	UHRF1	protein	For the NIH3T3 cells expressing wild-type UHRF1, most cells (∼74.6%) showed a focal pattern of protein that is co-localized with 4,6-diamidino-2-phenylindole (DAPI) foci (Fig. 5d), whereas the rest cells showed a diffuse nuclear staining pattern.	RESULTS
129	157	4,6-diamidino-2-phenylindole	chemical	For the NIH3T3 cells expressing wild-type UHRF1, most cells (∼74.6%) showed a focal pattern of protein that is co-localized with 4,6-diamidino-2-phenylindole (DAPI) foci (Fig. 5d), whereas the rest cells showed a diffuse nuclear staining pattern.	RESULTS
159	163	DAPI	chemical	For the NIH3T3 cells expressing wild-type UHRF1, most cells (∼74.6%) showed a focal pattern of protein that is co-localized with 4,6-diamidino-2-phenylindole (DAPI) foci (Fig. 5d), whereas the rest cells showed a diffuse nuclear staining pattern.	RESULTS
56	61	UHRF1	protein	The result is consistent with the previous studies that UHRF1 is mainly localized to highly methylated pericentromeric heterochromatin (PCH).	RESULTS
85	102	highly methylated	protein_state	The result is consistent with the previous studies that UHRF1 is mainly localized to highly methylated pericentromeric heterochromatin (PCH).	RESULTS
38	51	UHRF1Δ627–674	mutant	In contrast, for the cells expressing UHRF1Δ627–674, a spacer deletion mutant with decreased hm-DNA-binding affinity (Fig. 5b), only ∼22.1% cells showed co-localization with DAPI.	RESULTS
55	77	spacer deletion mutant	protein_state	In contrast, for the cells expressing UHRF1Δ627–674, a spacer deletion mutant with decreased hm-DNA-binding affinity (Fig. 5b), only ∼22.1% cells showed co-localization with DAPI.	RESULTS
93	116	hm-DNA-binding affinity	evidence	In contrast, for the cells expressing UHRF1Δ627–674, a spacer deletion mutant with decreased hm-DNA-binding affinity (Fig. 5b), only ∼22.1% cells showed co-localization with DAPI.	RESULTS
174	178	DAPI	chemical	In contrast, for the cells expressing UHRF1Δ627–674, a spacer deletion mutant with decreased hm-DNA-binding affinity (Fig. 5b), only ∼22.1% cells showed co-localization with DAPI.	RESULTS
37	39	H3	protein_type	Previous reports have shown that the H3K9me3 recognition of UHRF1 also plays an important role in its heterochromatin localization.	RESULTS
39	44	K9me3	ptm	Previous reports have shown that the H3K9me3 recognition of UHRF1 also plays an important role in its heterochromatin localization.	RESULTS
60	65	UHRF1	protein	Previous reports have shown that the H3K9me3 recognition of UHRF1 also plays an important role in its heterochromatin localization.	RESULTS
13	18	UHRF1	protein	For example, UHRF1 mutant (within TTD domain) lacking H3K9me3-binding affinity largely reduces its co-localization with heterochromatin.	RESULTS
19	25	mutant	protein_state	For example, UHRF1 mutant (within TTD domain) lacking H3K9me3-binding affinity largely reduces its co-localization with heterochromatin.	RESULTS
34	37	TTD	structure_element	For example, UHRF1 mutant (within TTD domain) lacking H3K9me3-binding affinity largely reduces its co-localization with heterochromatin.	RESULTS
46	53	lacking	protein_state	For example, UHRF1 mutant (within TTD domain) lacking H3K9me3-binding affinity largely reduces its co-localization with heterochromatin.	RESULTS
54	78	H3K9me3-binding affinity	evidence	For example, UHRF1 mutant (within TTD domain) lacking H3K9me3-binding affinity largely reduces its co-localization with heterochromatin.	RESULTS
35	41	hm-DNA	chemical	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
87	96	UHRF1ΔSRA	mutant	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
98	103	lacks	protein_state	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
104	127	hm-DNA-binding affinity	evidence	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
142	148	closed	protein_state	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
195	201	closed	protein_state	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
218	223	UHRF1	protein	Because manipulation of endogenous hm-DNA in cells is technically challenging, we used UHRF1ΔSRA (lacks hm-DNA-binding affinity but maintains closed conformation, Figs 3h and 5b) to test whether closed conformation of UHRF1 exists in vivo.	RESULTS
17	26	UHRF1ΔSRA	mutant	In NIH3T3 cells, UHRF1ΔSRA largely decreased chromatin association (Fig. 5d).	RESULTS
28	37	UHRF1ΔSRA	mutant	Only ∼4.8% cells expressing UHRF1ΔSRA showed an intermediate enrichment, but not characteristic focal pattern, at DAPI foci, whereas the majority of the cells showed a diffuse nuclear staining pattern.	RESULTS
114	118	DAPI	chemical	Only ∼4.8% cells expressing UHRF1ΔSRA showed an intermediate enrichment, but not characteristic focal pattern, at DAPI foci, whereas the majority of the cells showed a diffuse nuclear staining pattern.	RESULTS
25	34	UHRF1ΔSRA	mutant	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
42	48	closed	protein_state	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
70	72	H3	protein_type	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
72	77	K9me3	ptm	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
93	100	TTD–PHD	structure_element	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
186	192	Spacer	structure_element	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
216	221	UHRF1	protein	The results suggest that UHRF1ΔSRA adopts closed conformation so that H3K9me3 recognition by TTD–PHD is blocked by the intramolecular interaction, and support the regulatory role of the Spacer in PCH localization of UHRF1 in vivo.	RESULTS
4	10	spacer	structure_element	The spacer facilitates UHRF1–DNMT1 interaction	RESULTS
23	34	UHRF1–DNMT1	complex_assembly	The spacer facilitates UHRF1–DNMT1 interaction	RESULTS
27	32	UHRF1	protein	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
42	47	DNMT1	protein	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
51	57	hm-DNA	chemical	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
74	77	DNA	chemical	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
78	89	methylation	ptm	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
126	129	SRA	structure_element	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
134	143	RFTSDNMT1	protein	Previous studies show that UHRF1 recruits DNMT1 to hm-DNA for maintenance DNA methylation through the interaction between the SRA and RFTSDNMT1 (refs).	RESULTS
44	53	RFTSDNMT1	protein	We confirmed the direct interaction between RFTSDNMT1 and the SRA in a solution with low salt concentration (50 mM NaCl), but observed weak or undetectable interaction in a solution with higher salt concentrations (100 or 150 mM NaCl) (Supplementary Fig. 8a).	RESULTS
62	65	SRA	structure_element	We confirmed the direct interaction between RFTSDNMT1 and the SRA in a solution with low salt concentration (50 mM NaCl), but observed weak or undetectable interaction in a solution with higher salt concentrations (100 or 150 mM NaCl) (Supplementary Fig. 8a).	RESULTS
115	119	NaCl	chemical	We confirmed the direct interaction between RFTSDNMT1 and the SRA in a solution with low salt concentration (50 mM NaCl), but observed weak or undetectable interaction in a solution with higher salt concentrations (100 or 150 mM NaCl) (Supplementary Fig. 8a).	RESULTS
229	233	NaCl	chemical	We confirmed the direct interaction between RFTSDNMT1 and the SRA in a solution with low salt concentration (50 mM NaCl), but observed weak or undetectable interaction in a solution with higher salt concentrations (100 or 150 mM NaCl) (Supplementary Fig. 8a).	RESULTS
18	21	SRA	structure_element	Compared with the SRA, SRA–Spacer exhibited stronger interaction with RFTSDNMT1.	RESULTS
23	33	SRA–Spacer	structure_element	Compared with the SRA, SRA–Spacer exhibited stronger interaction with RFTSDNMT1.	RESULTS
70	79	RFTSDNMT1	protein	Compared with the SRA, SRA–Spacer exhibited stronger interaction with RFTSDNMT1.	RESULTS
13	22	RFTSDNMT1	protein	In addition, RFTSDNMT1 bound to SRA–Spacer with a binding affinity of 7.09 μM, but showed no detectable interaction with the SRA (Supplementary Fig. 8b).	RESULTS
23	31	bound to	protein_state	In addition, RFTSDNMT1 bound to SRA–Spacer with a binding affinity of 7.09 μM, but showed no detectable interaction with the SRA (Supplementary Fig. 8b).	RESULTS
32	42	SRA–Spacer	structure_element	In addition, RFTSDNMT1 bound to SRA–Spacer with a binding affinity of 7.09 μM, but showed no detectable interaction with the SRA (Supplementary Fig. 8b).	RESULTS
50	66	binding affinity	evidence	In addition, RFTSDNMT1 bound to SRA–Spacer with a binding affinity of 7.09 μM, but showed no detectable interaction with the SRA (Supplementary Fig. 8b).	RESULTS
125	128	SRA	structure_element	In addition, RFTSDNMT1 bound to SRA–Spacer with a binding affinity of 7.09 μM, but showed no detectable interaction with the SRA (Supplementary Fig. 8b).	RESULTS
31	37	hm-DNA	chemical	Interestingly, the addition of hm-DNA abolished the interaction between RFTSDNMT1 and SRA–Spacer, suggesting that hm-DNA also regulates UHRF1–DNMT1 interaction (Supplementary Fig. 8c).	RESULTS
72	81	RFTSDNMT1	protein	Interestingly, the addition of hm-DNA abolished the interaction between RFTSDNMT1 and SRA–Spacer, suggesting that hm-DNA also regulates UHRF1–DNMT1 interaction (Supplementary Fig. 8c).	RESULTS
86	96	SRA–Spacer	structure_element	Interestingly, the addition of hm-DNA abolished the interaction between RFTSDNMT1 and SRA–Spacer, suggesting that hm-DNA also regulates UHRF1–DNMT1 interaction (Supplementary Fig. 8c).	RESULTS
114	120	hm-DNA	chemical	Interestingly, the addition of hm-DNA abolished the interaction between RFTSDNMT1 and SRA–Spacer, suggesting that hm-DNA also regulates UHRF1–DNMT1 interaction (Supplementary Fig. 8c).	RESULTS
136	147	UHRF1–DNMT1	complex_assembly	Interestingly, the addition of hm-DNA abolished the interaction between RFTSDNMT1 and SRA–Spacer, suggesting that hm-DNA also regulates UHRF1–DNMT1 interaction (Supplementary Fig. 8c).	RESULTS
32	38	Spacer	structure_element	These results indicate that the Spacer facilitates the interaction between RFTSDNMT1 and the SRA, and the interaction is impaired by the presence of hm-DNA.	RESULTS
75	84	RFTSDNMT1	protein	These results indicate that the Spacer facilitates the interaction between RFTSDNMT1 and the SRA, and the interaction is impaired by the presence of hm-DNA.	RESULTS
93	96	SRA	structure_element	These results indicate that the Spacer facilitates the interaction between RFTSDNMT1 and the SRA, and the interaction is impaired by the presence of hm-DNA.	RESULTS
137	148	presence of	protein_state	These results indicate that the Spacer facilitates the interaction between RFTSDNMT1 and the SRA, and the interaction is impaired by the presence of hm-DNA.	RESULTS
149	155	hm-DNA	chemical	These results indicate that the Spacer facilitates the interaction between RFTSDNMT1 and the SRA, and the interaction is impaired by the presence of hm-DNA.	RESULTS
27	38	UHRF1–DNMT1	complex_assembly	We next tested whether the UHRF1–DNMT1 interaction is regulated by the conformational change of UHRF1.	RESULTS
96	101	UHRF1	protein	We next tested whether the UHRF1–DNMT1 interaction is regulated by the conformational change of UHRF1.	RESULTS
24	30	hm-DNA	chemical	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
68	78	SRA–Spacer	structure_element	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
83	92	RFTSDNMT1	protein	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
110	121	truncations	experimental_method	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
131	135	open	protein_state	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
140	146	closed	protein_state	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
156	161	UHRF1	protein	Because the addition of hm-DNA disrupts the interaction between the SRA–Spacer and RFTSDNMT1, we used various truncations to mimic open and closed forms of UHRF1.	RESULTS
7	17	absence of	protein_state	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
18	24	hm-DNA	chemical	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
31	40	UHRF1ΔTTD	mutant	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
41	49	bound to	protein_state	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
50	59	RFTSDNMT1	protein	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
69	80	full-length	protein_state	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
81	86	UHRF1	protein	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
88	97	UHRF1ΔSRA	mutant	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
102	115	UHRF1Δ627–674	mutant	In the absence of hm-DNA, only UHRF1ΔTTD bound to RFTSDNMT1, whereas full-length UHRF1, UHRF1ΔSRA and UHRF1Δ627–674 showed undetectable interaction (Fig. 5e).	RESULTS
7	18	deletion of	experimental_method	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
23	26	TTD	structure_element	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
34	39	UHRF1	protein	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
52	56	open	protein_state	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
96	105	RFTSDNMT1	protein	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
106	114	binds to	protein_state	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
115	125	SRA–Spacer	structure_element	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
131	136	UHRF1	protein	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
147	151	open	protein_state	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
172	182	absence of	protein_state	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
183	189	hm-DNA	chemical	As the deletion of the TTD allows UHRF1 to adopt an open conformation, the results suggest that RFTSDNMT1 binds to SRA–Spacer when UHRF1 adopts an open conformation in the absence of hm-DNA.	RESULTS
38	46	addition	experimental_method	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
66	75	RFTSDNMT1	protein	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
109	114	UHRF1	protein	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
119	125	hm-DNA	chemical	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
206	218	UHRF1–hm-DNA	complex_assembly	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
223	234	UHRF1–DNMT1	complex_assembly	In support of above observations, the addition of large amount of RFTSDNMT1 impaired the interaction between UHRF1 and hm-DNA (Supplementary Fig. 8d), suggesting an existence of dynamic equilibrium between UHRF1–hm-DNA and UHRF1–DNMT1 complexes.	RESULTS
69	75	hm-DNA	chemical	According to the above results, we here proposed a working model for hm-DNA-mediated regulation of UHRF1 conformation (Fig. 5f).	DISCUSS
99	104	UHRF1	protein	According to the above results, we here proposed a working model for hm-DNA-mediated regulation of UHRF1 conformation (Fig. 5f).	DISCUSS
7	17	absence of	protein_state	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
18	24	hm-DNA	chemical	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
30	35	UHRF1	protein	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
46	52	closed	protein_state	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
80	86	Spacer	structure_element	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
87	95	binds to	protein_state	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
100	103	TTD	structure_element	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
126	132	Linker	structure_element	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
141	144	SRA	structure_element	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
145	153	binds to	protein_state	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
158	161	PHD	structure_element	In the absence of hm-DNA (A), UHRF1 prefers a closed conformation, in which the Spacer binds to the TTD by competing with the Linker and the SRA binds to the PHD.	DISCUSS
32	39	histone	protein_type	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
40	42	H3	protein_type	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
42	47	K9me3	ptm	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
55	58	TTD	structure_element	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
77	83	Spacer	structure_element	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
104	114	unmodified	protein_state	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
115	122	histone	protein_type	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
123	125	H3	protein_type	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
127	131	H3R2	site	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
140	143	PHD	structure_element	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
164	167	SRA	structure_element	As a result, the recognition of histone H3K9me3 by the TTD is blocked by the Spacer, and recognition of unmodified histone H3 (H3R2) by the PHD is inhibited by the SRA.	DISCUSS
24	29	UHRF1	protein	The interaction between UHRF1 and DNMT1 is also weak because the Spacer is unable to facilitate the intermolecular interaction.	DISCUSS
34	39	DNMT1	protein	The interaction between UHRF1 and DNMT1 is also weak because the Spacer is unable to facilitate the intermolecular interaction.	DISCUSS
65	71	Spacer	structure_element	The interaction between UHRF1 and DNMT1 is also weak because the Spacer is unable to facilitate the intermolecular interaction.	DISCUSS
7	18	presence of	protein_state	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
19	25	hm-DNA	chemical	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
31	36	UHRF1	protein	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
48	52	open	protein_state	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
80	83	SRA	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
84	92	binds to	protein_state	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
97	103	hm-DNA	chemical	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
109	115	Spacer	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
137	140	TTD	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
185	188	SRA	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
193	199	hm-DNA	chemical	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
205	211	Linker	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
212	220	binds to	protein_state	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
225	228	TTD	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
240	247	TTD–PHD	structure_element	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
261	268	histone	protein_type	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
269	271	H3	protein_type	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
271	276	K9me3	ptm	In the presence of hm-DNA (B), UHRF1 prefers an open conformation, in which the SRA binds to the hm-DNA; the Spacer dissociates from the TTD and facilitates the interaction between the SRA and hm-DNA; the Linker binds to the TTD and allows TTD–PHD to recognize histone H3K9me3.	DISCUSS
5	10	UHRF1	protein	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
21	25	open	protein_state	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
55	63	bound to	protein_state	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
64	66	H3	protein_type	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
66	71	K9me3	ptm	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
101	103	H3	protein_type	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
103	108	K9me3	ptm	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
113	120	TTD–PHD	structure_element	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
142	148	Spacer	structure_element	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
188	191	TTD	structure_element	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
213	218	UHRF1	protein	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
225	229	open	protein_state	When UHRF1 adopts an open conformation and has already bound to H3K9me3 (B), the interaction between H3K9me3 and TTD–PHD further prevents the Spacer from folding back to interact with the TTD, and therefore locks UHRF1 in an open conformation.	DISCUSS
19	24	UHRF1	protein	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
32	39	histone	protein_type	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
59	73	ubiquitination	ptm	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
77	84	histone	protein_type	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
103	107	RING	structure_element	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
120	125	DNMT1	protein	The association of UHRF1 to the histone may facilitate the ubiquitination of histone tail (mediated by RING domain) for DNMT1 targeting.	DISCUSS
58	63	DNMT1	protein	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
72	78	hm-DNA	chemical	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
99	110	methylation	ptm	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
150	157	histone	protein_type	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
158	172	ubiquitylation	ptm	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
180	190	SRA-Spacer	structure_element	Moreover, through a mechanism yet to be fully elucidated, DNMT1 targets hm-DNA for maintenance DNA methylation, probably through interaction with the histone ubiquitylation and/or SRA-Spacer.	DISCUSS
4	17	P(r) function	evidence	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
32	60	small-angle X-ray scattering	experimental_method	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
62	66	SAXS	experimental_method	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
84	109	TTD–PHD–SRA–Spacer–hm-DNA	complex_assembly	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
165	183	TTD–PHD–SRA–Spacer	complex_assembly	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
226	231	UHRF1	protein	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
242	246	open	protein_state	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
267	278	presence of	protein_state	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
279	285	hm-DNA	chemical	The P(r) function obtained from small-angle X-ray scattering (SAXS) measurements of TTD–PHD–SRA–Spacer–hm-DNA complex showed a broader distribution than that of the TTD–PHD–SRA–Spacer alone, supporting the proposed model that UHRF1 adopts an open conformation in the presence of hm-DNA (Supplementary Fig. 8e).	DISCUSS
14	27	crystallizing	experimental_method	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
59	63	with	protein_state	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
68	75	without	protein_state	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
76	79	DNA	chemical	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
153	162	structure	evidence	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
166	184	TTD–PHD–SRA–Spacer	complex_assembly	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
192	199	absence	protein_state	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
203	214	presence of	protein_state	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
215	221	hm-DNA	chemical	We have tried crystallizing more than three sub-constructs with and without DNA across over 1,200 crystallization conditions but failed to determine the structure of TTD–PHD–SRA–Spacer in the absence or presence of hm-DNA.	DISCUSS
14	24	structures	evidence	Getting these structures would greatly help for understanding the hm-DNA-mediated regulation of UHRF1.	DISCUSS
66	72	hm-DNA	chemical	Getting these structures would greatly help for understanding the hm-DNA-mediated regulation of UHRF1.	DISCUSS
96	101	UHRF1	protein	Getting these structures would greatly help for understanding the hm-DNA-mediated regulation of UHRF1.	DISCUSS
104	132	single molecular measurement	experimental_method	In addition, this regulatory process should be further characterized using advanced techniques, such as single molecular measurement.	DISCUSS
31	46	phosphorylation	ptm	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
50	54	S639	residue_name_number	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
66	72	Spacer	structure_element	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
102	107	UHRF1	protein	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
112	126	deubiquitylase	protein_type	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
127	131	USP7	protein	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
146	151	UHRF1	protein	Our previous studies show that phosphorylation at S639 within the Spacer disrupts interaction between UHRF1 and deubiquitylase USP7 and decreases UHRF1 stability in the M phase of the cell cycle.	DISCUSS
4	10	Spacer	structure_element	The Spacer was predicted to contain two nuclear localization signals, residues 581–600 and 648-670 (ref.).	DISCUSS
40	68	nuclear localization signals	structure_element	The Spacer was predicted to contain two nuclear localization signals, residues 581–600 and 648-670 (ref.).	DISCUSS
79	86	581–600	residue_range	The Spacer was predicted to contain two nuclear localization signals, residues 581–600 and 648-670 (ref.).	DISCUSS
91	98	648-670	residue_range	The Spacer was predicted to contain two nuclear localization signals, residues 581–600 and 648-670 (ref.).	DISCUSS
34	40	Spacer	structure_element	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
45	53	binds to	protein_state	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
58	61	TTD	structure_element	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
69	75	closed	protein_state	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
84	89	UHRF1	protein	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
124	126	H3	protein_type	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
126	131	K9me3	ptm	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
150	156	hm-DNA	chemical	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
176	179	SRA	structure_element	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
230	233	SRA	structure_element	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
238	247	RFTSDNMT1	protein	In this report, we found that the Spacer (i) binds to the TTD in the closed form of UHRF1 and inhibits its interaction with H3K9me3; (ii) facilitates hm-DNA recognition by the SRA and (iii) facilitates the interaction between the SRA and RFTSDNMT1.	DISCUSS
42	48	Spacer	structure_element	These findings together indicate that the Spacer plays a very important role in the dynamic regulation of UHRF1.	DISCUSS
106	111	UHRF1	protein	These findings together indicate that the Spacer plays a very important role in the dynamic regulation of UHRF1.	DISCUSS
79	83	PI5P	chemical	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
91	97	Spacer	structure_element	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
108	114	closed	protein_state	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
131	136	UHRF1	protein	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
151	175	H3K9me3-binding affinity	evidence	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
183	186	TTD	structure_element	When our manuscript was in preparation, Gelato et al. reported that binding of PI5P to the Spacer opens the closed conformation of UHRF1 and increases H3K9me3-binding affinity of the TTD.	DISCUSS
25	29	PI5P	chemical	The result suggests that PI5P may facilitate the conformational change of UHRF1 induced by hm-DNA when UHRF1 is recruited to chromatin.	DISCUSS
74	79	UHRF1	protein	The result suggests that PI5P may facilitate the conformational change of UHRF1 induced by hm-DNA when UHRF1 is recruited to chromatin.	DISCUSS
91	97	hm-DNA	chemical	The result suggests that PI5P may facilitate the conformational change of UHRF1 induced by hm-DNA when UHRF1 is recruited to chromatin.	DISCUSS
103	108	UHRF1	protein	The result suggests that PI5P may facilitate the conformational change of UHRF1 induced by hm-DNA when UHRF1 is recruited to chromatin.	DISCUSS
13	30	mass-spectrometry	experimental_method	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
64	85	phosphorylation sites	site	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
87	91	S639	residue_name_number	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
93	97	S651	residue_name_number	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
99	103	S661	residue_name_number	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
116	122	Spacer	structure_element	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
211	216	UHRF1	protein	In addition, mass-spectrometry analyses have identified several phosphorylation sites (S639, S651, S661) within the Spacer, suggesting that post-translational modification may add another layer of regulation of UHRF1 (refs).	DISCUSS
40	43	SRA	structure_element	It has been well characterized that the SRA of UHRF1 preferentially recognizes hm-DNA through a base-flipping mechanism.	DISCUSS
47	52	UHRF1	protein	It has been well characterized that the SRA of UHRF1 preferentially recognizes hm-DNA through a base-flipping mechanism.	DISCUSS
79	85	hm-DNA	chemical	It has been well characterized that the SRA of UHRF1 preferentially recognizes hm-DNA through a base-flipping mechanism.	DISCUSS
32	38	Spacer	structure_element	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
61	84	hm-DNA-binding affinity	evidence	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
92	95	SRA	structure_element	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
104	115	deletion of	experimental_method	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
120	126	Spacer	structure_element	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
167	172	UHRF1	protein	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
194	200	Spacer	structure_element	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
233	239	hm-DNA	chemical	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
258	269	full-length	protein_state	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
270	275	UHRF1	protein	Our study demonstrates that the Spacer markedly enhances the hm-DNA-binding affinity of the SRA and the deletion of the Spacer impairs heterochromatin localization of UHRF1, indicating that the Spacer is essential for recognition of hm-DNA in the context of full-length UHRF1.	DISCUSS
15	39	variant in methylation 1	protein	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
41	45	VIM1	protein	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
49	54	UHRF1	protein	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
68	79	Arabidopsis	taxonomy_domain	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
104	110	spacer	structure_element	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
154	160	hm-DNA	chemical	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
180	183	SRA	structure_element	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
239	242	SRA	structure_element	Interestingly, variant in methylation 1 (VIM1, a UHRF1 homologue in Arabidopsis) contains an equivalent spacer region, which was shown to be required for hm-DNA recognition by its SRA domain, suggesting a conserved regulatory mechanism in SRA domain-containing proteins.	DISCUSS
14	19	UHRF2	protein	Intriguingly, UHRF2 (the only mammalian homologue of UHRF1) and UHRF1 show very high sequence similarities for all the domains but very low similarity for the Spacer (Supplementary Fig. 7c).	DISCUSS
30	39	mammalian	taxonomy_domain	Intriguingly, UHRF2 (the only mammalian homologue of UHRF1) and UHRF1 show very high sequence similarities for all the domains but very low similarity for the Spacer (Supplementary Fig. 7c).	DISCUSS
53	58	UHRF1	protein	Intriguingly, UHRF2 (the only mammalian homologue of UHRF1) and UHRF1 show very high sequence similarities for all the domains but very low similarity for the Spacer (Supplementary Fig. 7c).	DISCUSS
64	69	UHRF1	protein	Intriguingly, UHRF2 (the only mammalian homologue of UHRF1) and UHRF1 show very high sequence similarities for all the domains but very low similarity for the Spacer (Supplementary Fig. 7c).	DISCUSS
159	165	Spacer	structure_element	Intriguingly, UHRF2 (the only mammalian homologue of UHRF1) and UHRF1 show very high sequence similarities for all the domains but very low similarity for the Spacer (Supplementary Fig. 7c).	DISCUSS
15	20	UHRF2	protein	Thus, although UHRF2 exhibits the histone- and hm-DNA-binding activities, the difference in the Spacer region may contribute to the functional differences between UHRF1 and UHRF2.	DISCUSS
96	102	Spacer	structure_element	Thus, although UHRF2 exhibits the histone- and hm-DNA-binding activities, the difference in the Spacer region may contribute to the functional differences between UHRF1 and UHRF2.	DISCUSS
163	168	UHRF1	protein	Thus, although UHRF2 exhibits the histone- and hm-DNA-binding activities, the difference in the Spacer region may contribute to the functional differences between UHRF1 and UHRF2.	DISCUSS
173	178	UHRF2	protein	Thus, although UHRF2 exhibits the histone- and hm-DNA-binding activities, the difference in the Spacer region may contribute to the functional differences between UHRF1 and UHRF2.	DISCUSS
51	56	UHRF2	protein	This is also consistent with previous finding that UHRF2 is unable to replace UHRF1 to maintain the DNA methylation.	DISCUSS
78	83	UHRF1	protein	This is also consistent with previous finding that UHRF2 is unable to replace UHRF1 to maintain the DNA methylation.	DISCUSS
100	103	DNA	chemical	This is also consistent with previous finding that UHRF2 is unable to replace UHRF1 to maintain the DNA methylation.	DISCUSS
104	115	methylation	ptm	This is also consistent with previous finding that UHRF2 is unable to replace UHRF1 to maintain the DNA methylation.	DISCUSS
41	44	DNA	chemical	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
45	56	methylation	ptm	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
64	69	UHRF1	protein	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
132	134	H3	protein_type	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
134	139	K9me3	ptm	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
144	151	TTD–PHD	structure_element	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
157	163	hm-DNA	chemical	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
172	175	SRA	structure_element	One of the key questions in the field of DNA methylation is why UHRF1 contains modules recognizing two repressive epigenetic marks: H3K9me3 (by TTD–PHD) and hm-DNA (by the SRA).	DISCUSS
53	58	UHRF1	protein	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
75	81	hm-DNA	chemical	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
119	126	histone	protein_type	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
127	129	H3	protein_type	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
129	134	K9me3	ptm	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
151	157	hm-DNA	chemical	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
192	197	UHRF1	protein	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
219	222	DNA	chemical	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
223	234	methylation	ptm	Previous studies show that chromatin localization of UHRF1 is dependent on hm-DNA, whereas other studies indicate that histone H3K9me3 recognition and hm-DNA association are both required for UHRF1-mediated maintenance DNA methylation.	DISCUSS
87	92	UHRF1	protein	However, little is known about the crosstalk between these two epigenetic marks within UHRF1.	DISCUSS
47	49	H3	protein_type	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
49	54	K9me3	ptm	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
58	69	full-length	protein_state	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
70	75	UHRF1	protein	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
121	133	unmethylated	protein_state	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
178	180	H3	protein_type	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
180	185	K9me3	ptm	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
187	189	KD	evidence	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
202	204	H3	protein_type	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
204	209	K9me0	ptm	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
211	213	KD	evidence	As shown in the proposed model, recognition of H3K9me3 by full-length UHRF1 is blocked to avoid its miss-localization to unmethylated genomic region, in which chromatin contains H3K9me3 (KD=4.61 μM) or H3K9me0 (KD=25.99 μM).	DISCUSS
19	30	full-length	protein_state	We have shown that full-length UHRF1 and SRA–Spacer strongly bind to hm-DNA (0.35 and 0.49 μM, respectively) and the Spacer plays an important role in PCH localization (Fig. 5d).	DISCUSS
31	36	UHRF1	protein	We have shown that full-length UHRF1 and SRA–Spacer strongly bind to hm-DNA (0.35 and 0.49 μM, respectively) and the Spacer plays an important role in PCH localization (Fig. 5d).	DISCUSS
41	51	SRA–Spacer	structure_element	We have shown that full-length UHRF1 and SRA–Spacer strongly bind to hm-DNA (0.35 and 0.49 μM, respectively) and the Spacer plays an important role in PCH localization (Fig. 5d).	DISCUSS
69	75	hm-DNA	chemical	We have shown that full-length UHRF1 and SRA–Spacer strongly bind to hm-DNA (0.35 and 0.49 μM, respectively) and the Spacer plays an important role in PCH localization (Fig. 5d).	DISCUSS
117	123	Spacer	structure_element	We have shown that full-length UHRF1 and SRA–Spacer strongly bind to hm-DNA (0.35 and 0.49 μM, respectively) and the Spacer plays an important role in PCH localization (Fig. 5d).	DISCUSS
35	40	UHRF1	protein	Therefore, genomic localization of UHRF1 is primarily determined by its recognition of hm-DNA, which allows UHRF1 to adopt an open form and promotes its histone tail recognition for proper genomic localization and function.	DISCUSS
87	93	hm-DNA	chemical	Therefore, genomic localization of UHRF1 is primarily determined by its recognition of hm-DNA, which allows UHRF1 to adopt an open form and promotes its histone tail recognition for proper genomic localization and function.	DISCUSS
108	113	UHRF1	protein	Therefore, genomic localization of UHRF1 is primarily determined by its recognition of hm-DNA, which allows UHRF1 to adopt an open form and promotes its histone tail recognition for proper genomic localization and function.	DISCUSS
126	130	open	protein_state	Therefore, genomic localization of UHRF1 is primarily determined by its recognition of hm-DNA, which allows UHRF1 to adopt an open form and promotes its histone tail recognition for proper genomic localization and function.	DISCUSS
153	160	histone	protein_type	Therefore, genomic localization of UHRF1 is primarily determined by its recognition of hm-DNA, which allows UHRF1 to adopt an open form and promotes its histone tail recognition for proper genomic localization and function.	DISCUSS
18	28	SRA–Spacer	structure_element	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
46	52	hm-DNA	chemical	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
57	65	binds to	protein_state	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
66	71	DNMT1	protein	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
108	113	UHRF1	protein	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
193	200	TTD–PHD	structure_element	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
205	207	H3	protein_type	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
207	212	K9me3	ptm	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
217	220	PHD	structure_element	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
221	223	H3	protein_type	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
251	256	DNMT1	protein	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
274	277	DNA	chemical	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
292	303	methylation	ptm	As a result, when SRA–Spacer dissociates from hm-DNA and binds to DNMT1 with a currently unknown mechanism, UHRF1 may keep the complex associated with chromatin through the interaction between TTD–PHD and H3K9me3 (or PHD-H3), and make it possible for DNMT1 to target proper DNA substrate for methylation.	DISCUSS
116	118	H3	protein_type	This explanation agrees nicely with previous observations and clarifies the importance of coordinate recognition of H3K9me3 and hm-DNA by UHRF1 for maintenance DNA methylation.	DISCUSS
118	123	K9me3	ptm	This explanation agrees nicely with previous observations and clarifies the importance of coordinate recognition of H3K9me3 and hm-DNA by UHRF1 for maintenance DNA methylation.	DISCUSS
128	134	hm-DNA	chemical	This explanation agrees nicely with previous observations and clarifies the importance of coordinate recognition of H3K9me3 and hm-DNA by UHRF1 for maintenance DNA methylation.	DISCUSS
138	143	UHRF1	protein	This explanation agrees nicely with previous observations and clarifies the importance of coordinate recognition of H3K9me3 and hm-DNA by UHRF1 for maintenance DNA methylation.	DISCUSS
164	175	methylation	ptm	This explanation agrees nicely with previous observations and clarifies the importance of coordinate recognition of H3K9me3 and hm-DNA by UHRF1 for maintenance DNA methylation.	DISCUSS
0	5	UHRF1	protein	UHRF1 is essential for maintenance DNA methylation through recruiting DNMT1 to DNA replication forks during S phase.	DISCUSS
35	38	DNA	chemical	UHRF1 is essential for maintenance DNA methylation through recruiting DNMT1 to DNA replication forks during S phase.	DISCUSS
39	50	methylation	ptm	UHRF1 is essential for maintenance DNA methylation through recruiting DNMT1 to DNA replication forks during S phase.	DISCUSS
70	75	DNMT1	protein	UHRF1 is essential for maintenance DNA methylation through recruiting DNMT1 to DNA replication forks during S phase.	DISCUSS
79	82	DNA	chemical	UHRF1 is essential for maintenance DNA methylation through recruiting DNMT1 to DNA replication forks during S phase.	DISCUSS
70	73	SRA	structure_element	This function is probably induced by a direct interaction between the SRA and RFTSDNMT1 (refs) or interaction between DNMT1 and ubiquitylation of histione tail.	DISCUSS
78	87	RFTSDNMT1	protein	This function is probably induced by a direct interaction between the SRA and RFTSDNMT1 (refs) or interaction between DNMT1 and ubiquitylation of histione tail.	DISCUSS
118	123	DNMT1	protein	This function is probably induced by a direct interaction between the SRA and RFTSDNMT1 (refs) or interaction between DNMT1 and ubiquitylation of histione tail.	DISCUSS
128	142	ubiquitylation	ptm	This function is probably induced by a direct interaction between the SRA and RFTSDNMT1 (refs) or interaction between DNMT1 and ubiquitylation of histione tail.	DISCUSS
146	154	histione	protein_type	This function is probably induced by a direct interaction between the SRA and RFTSDNMT1 (refs) or interaction between DNMT1 and ubiquitylation of histione tail.	DISCUSS
28	35	histone	protein_type	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
56	61	UHRF1	protein	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
70	73	PHD	structure_element	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
98	105	histone	protein_type	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
106	108	H3	protein_type	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
109	123	ubiquitylation	ptm	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
147	163	ubiquitin ligase	protein_type	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
180	184	RING	structure_element	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
195	200	UHRF1	protein	Recent study indicates that histone tail association of UHRF1 (by the PHD domain) is required for histone H3 ubiquitylation, which is dependent on ubiquitin ligase activity of the RING domain of UHRF1 (ref.).	DISCUSS
0	5	DNMT1	protein	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
6	14	binds to	protein_state	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
15	28	ubiquitylated	protein_state	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
29	36	histone	protein_type	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
37	39	H3	protein_type	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
44	58	ubiquitylation	ptm	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
90	93	DNA	chemical	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
94	105	methylation	ptm	DNMT1 binds to ubiquitylated histone H3 and ubiquitylation is required for maintenance of DNA methylation in vivo.	DISCUSS
34	37	TTD	structure_element	In this study, we found that both TTD and PHD are regulated by hm-DNA to recognize histone tail.	DISCUSS
42	45	PHD	structure_element	In this study, we found that both TTD and PHD are regulated by hm-DNA to recognize histone tail.	DISCUSS
63	69	hm-DNA	chemical	In this study, we found that both TTD and PHD are regulated by hm-DNA to recognize histone tail.	DISCUSS
83	90	histone	protein_type	In this study, we found that both TTD and PHD are regulated by hm-DNA to recognize histone tail.	DISCUSS
10	16	closed	protein_state	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
22	27	UHRF1	protein	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
61	66	URHF1	protein	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
85	90	UHRF1	protein	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
94	98	open	protein_state	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
124	130	hm-DNA	chemical	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
147	155	binds to	protein_state	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
156	163	histone	protein_type	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
173	187	ubiquitylation	ptm	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
203	206	DNA	chemical	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
207	218	methylation	ptm	Thus, the closed form UHRF1 may prevent miss localization of URHF1, whereas only the UHRF1 in open conformation (induced by hm-DNA) could properly binds to histone tail for ubiquitylation and subsequent DNA methylation.	DISCUSS
10	29	structural analyses	experimental_method	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
33	42	DNMT1–DNA	complex_assembly	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
47	54	SRA–DNA	complex_assembly	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
105	110	DNMT1	protein	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
128	134	hm-DNA	chemical	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
140	145	UHRF1	protein	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
146	154	binds to	protein_state	Moreover, structural analyses of DNMT1–DNA and SRA–DNA complexes also indicate that it is impossible for DNMT1 to methylate the hm-DNA that UHRF1 binds to because of steric hindrance.	DISCUSS
7	22	in vitro assays	experimental_method	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
60	70	SRA–Spacer	structure_element	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
75	84	RFTSDNMT1	protein	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
118	129	full-length	protein_state	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
130	135	UHRF1	protein	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
140	149	RFTSDNMT1	protein	In our in vitro assays, we could detect interaction between SRA–Spacer and RFTSDNMT1, but not the interaction between full-length UHRF1 and RFTSDNMT1 (Supplementary Fig. 8a,b and Fig. 5e).	DISCUSS
25	30	UHRF1	protein	The results suggest that UHRF1 adopts multiple conformations.	DISCUSS
11	16	UHRF1	protein	Binding of UHRF1 to hm-DNA may serve as a switch for its recruitment of DNMT1.	DISCUSS
20	26	hm-DNA	chemical	Binding of UHRF1 to hm-DNA may serve as a switch for its recruitment of DNMT1.	DISCUSS
72	77	DNMT1	protein	Binding of UHRF1 to hm-DNA may serve as a switch for its recruitment of DNMT1.	DISCUSS
42	47	UHRF1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
52	57	DNMT1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
78	83	DNMT1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
130	139	RFTSDNMT1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
140	148	binds to	protein_state	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
149	154	UHRF1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
163	179	catalytic domain	structure_element	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
183	188	DNMT1	protein	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
189	197	binds to	protein_state	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
198	204	hm-DNA	chemical	The S phase-dependent interaction between UHRF1 and DNMT1 (refs) suggest that DNMT1 may also undergo conformation changes so that RFTSDNMT1 binds to UHRF1 and the catalytic domain of DNMT1 binds to hm-DNA for reaction.	DISCUSS
0	6	Hm-DNA	chemical	Hm-DNA facilities histione tails recognition by full-length UHRF1.	FIG
18	26	histione	protein_type	Hm-DNA facilities histione tails recognition by full-length UHRF1.	FIG
48	59	full-length	protein_state	Hm-DNA facilities histione tails recognition by full-length UHRF1.	FIG
60	65	UHRF1	protein	Hm-DNA facilities histione tails recognition by full-length UHRF1.	FIG
37	42	human	species	(a) Colour-coded domain structure of human UHRF1.	FIG
43	48	UHRF1	protein	(a) Colour-coded domain structure of human UHRF1.	FIG
14	23	conserved	protein_state	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
56	62	Linker	structure_element	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
73	80	286–306	residue_range	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
90	96	Spacer	structure_element	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
107	114	587–674	residue_range	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
128	131	TTD	structure_element	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
167	173	Hm-DNA	chemical	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
185	192	histone	protein_type	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
193	195	H3	protein_type	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
200	202	H3	protein_type	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
223	228	UHRF1	protein	Note that the conserved motif (green background) of the Linker (residues 286–306) and the Spacer (residues 587–674) bind to the TTD in a similar manner (Fig. 3b). (b) Hm-DNA facilities histone H3 and H3K9me3 recognition by UHRF1.	FIG
9	20	full-length	protein_state	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
21	26	UHRF1	protein	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
46	58	biotinylated	protein_state	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
59	61	H3	protein_type	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
63	67	1–21	residue_range	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
72	74	H3	protein_type	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
74	79	K9me3	ptm	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
81	85	1–21	residue_range	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
115	125	absence of	protein_state	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
126	132	hm-DNA	chemical	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
146	151	UHRF1	protein	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
152	158	hm-DNA	chemical	Purified full-length UHRF1 was incubated with biotinylated H3 (1–21) or H3K9me3 (1–21) peptides in the presence or absence of hm-DNA (molar ratio UHRF1/hm-DNA=1:2).	FIG
36	44	SDS–PAGE	experimental_method	The bound proteins were analysed in SDS–PAGE followed by Coomassie blue staining.	FIG
70	77	Histone	protein_type	Sequences of the peptides are indicated in Supplementary Table 1. (c) Histone peptides do not affect hm-DNA-binding affinity of UHRF1.	FIG
101	124	hm-DNA-binding affinity	evidence	Sequences of the peptides are indicated in Supplementary Table 1. (c) Histone peptides do not affect hm-DNA-binding affinity of UHRF1.	FIG
128	133	UHRF1	protein	Sequences of the peptides are indicated in Supplementary Table 1. (c) Histone peptides do not affect hm-DNA-binding affinity of UHRF1.	FIG
0	11	Full-length	protein_state	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
12	17	UHRF1	protein	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
22	36	incubated with	experimental_method	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
37	49	biotinylated	protein_state	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
50	56	hm-DNA	chemical	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
76	86	absence of	protein_state	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
87	89	H3	protein_type	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
91	95	1–17	residue_range	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
100	102	H3	protein_type	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
102	107	K9me3	ptm	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
109	113	1–17	residue_range	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
165	168	ITC	experimental_method	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
169	183	enthalpy plots	evidence	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
199	201	H3	protein_type	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
201	206	K9me3	ptm	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
216	220	1–17	residue_range	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
225	232	TTD–PHD	structure_element	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
237	248	full-length	protein_state	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
249	254	UHRF1	protein	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
264	266	H3	protein_type	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
276	280	1–17	residue_range	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
289	292	PHD	structure_element	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
297	308	full-length	protein_state	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
309	314	UHRF1	protein	Full-length UHRF1 was incubated with biotinylated hm-DNA in the presence or absence of H3 (1–17) or H3K9me3 (1–17) peptides and analysed as in b. (d,e) Superimposed ITC enthalpy plots for binding of H3K9me3 peptide (1–17) to TTD–PHD and full-length UHRF1 (d), and H3 peptide (1–17) to the PHD and full-length UHRF1 (e).	FIG
14	32	binding affinities	evidence	The estimated binding affinities (KD) are listed.	FIG
34	36	KD	evidence	The estimated binding affinities (KD) are listed.	FIG
36	43	histone	protein_type	Intramolecular interactions inhibit histone recognition by UHRF1.	FIG
59	64	UHRF1	protein	Intramolecular interactions inhibit histone recognition by UHRF1.	FIG
4	24	GST pull-down assays	experimental_method	(a) GST pull-down assays for the intramolecular interactions.	FIG
24	29	UHRF1	protein	The isolated domains of UHRF1 were incubated with GST-tagged TTD or PHD immobilized on glutathione resin.	FIG
35	44	incubated	experimental_method	The isolated domains of UHRF1 were incubated with GST-tagged TTD or PHD immobilized on glutathione resin.	FIG
50	60	GST-tagged	protein_state	The isolated domains of UHRF1 were incubated with GST-tagged TTD or PHD immobilized on glutathione resin.	FIG
61	64	TTD	structure_element	The isolated domains of UHRF1 were incubated with GST-tagged TTD or PHD immobilized on glutathione resin.	FIG
68	71	PHD	structure_element	The isolated domains of UHRF1 were incubated with GST-tagged TTD or PHD immobilized on glutathione resin.	FIG
36	44	SDS–PAGE	experimental_method	The bound proteins were analysed by SDS–PAGE and Coomassie blue staining.	FIG
36	44	SDS–PAGE	experimental_method	The bound proteins were analysed by SDS–PAGE and Coomassie blue staining.	FIG
19	22	ITC	experimental_method	(b,d) Superimposed ITC enthalpy plots for the intramolecular interactions of isolated UHRF1 domains.	FIG
23	37	enthalpy plots	evidence	(b,d) Superimposed ITC enthalpy plots for the intramolecular interactions of isolated UHRF1 domains.	FIG
86	91	UHRF1	protein	(b,d) Superimposed ITC enthalpy plots for the intramolecular interactions of isolated UHRF1 domains.	FIG
14	32	binding affinities	evidence	The estimated binding affinities (KD) were listed.	FIG
34	36	KD	evidence	The estimated binding affinities (KD) were listed.	FIG
37	40	ITC	experimental_method	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
41	55	enthalpy plots	evidence	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
75	77	H3	protein_type	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
77	82	K9me3	ptm	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
86	93	TTD–PHD	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
101	108	absence	protein_state	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
112	123	presence of	protein_state	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
128	134	Spacer	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
148	155	TTD–PHD	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
156	162	Spacer	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
186	189	ITC	experimental_method	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
190	204	enthalpy plots	evidence	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
224	226	H3	protein_type	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
230	237	PHD–SRA	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
241	244	PHD	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
252	259	absence	protein_state	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
263	274	presence of	protein_state	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
279	282	SRA	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
296	299	PHD	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
300	303	SRA	structure_element	ND, not detectable. (c) Superimposed ITC enthalpy plots for the binding of H3K9me3 to TTD–PHD in the absence or presence of the Spacer (molar ratio TTD–PHD/Spacer=1:2). (e) Superimposed ITC enthalpy plots for the binding of H3 to PHD–SRA or PHD in the absence or presence of the SRA (molar ratio PHD/SRA=1:1 or 1:2).	FIG
0	3	NMR	experimental_method	NMR structure of the TTD bound to the Spacer.	FIG
4	13	structure	evidence	NMR structure of the TTD bound to the Spacer.	FIG
21	24	TTD	structure_element	NMR structure of the TTD bound to the Spacer.	FIG
25	33	bound to	protein_state	NMR structure of the TTD bound to the Spacer.	FIG
38	44	Spacer	structure_element	NMR structure of the TTD bound to the Spacer.	FIG
29	39	TTD–Spacer	structure_element	(a) Ribbon representation of TTD–Spacer structure.	FIG
40	49	structure	evidence	(a) Ribbon representation of TTD–Spacer structure.	FIG
24	30	Spacer	structure_element	N- and C-termini of the Spacer are indicated.	FIG
4	7	TTD	structure_element	The TTD is coloured in green, and the Spacer is coloured in yellow.	FIG
38	44	Spacer	structure_element	The TTD is coloured in green, and the Spacer is coloured in yellow.	FIG
4	19	Superimposition	experimental_method	(b) Superimposition of TTD–Spacer and TTD–PHD–H3K9me3 (4GY5.PDB) structures shown in ribbon representations.	FIG
23	33	TTD–Spacer	structure_element	(b) Superimposition of TTD–Spacer and TTD–PHD–H3K9me3 (4GY5.PDB) structures shown in ribbon representations.	FIG
38	53	TTD–PHD–H3K9me3	complex_assembly	(b) Superimposition of TTD–Spacer and TTD–PHD–H3K9me3 (4GY5.PDB) structures shown in ribbon representations.	FIG
65	75	structures	evidence	(b) Superimposition of TTD–Spacer and TTD–PHD–H3K9me3 (4GY5.PDB) structures shown in ribbon representations.	FIG
4	7	TTD	structure_element	The TTD is coloured in green and the Spacer in yellow in TTD–Spacer structure.	FIG
37	43	Spacer	structure_element	The TTD is coloured in green and the Spacer in yellow in TTD–Spacer structure.	FIG
57	67	TTD–Spacer	structure_element	The TTD is coloured in green and the Spacer in yellow in TTD–Spacer structure.	FIG
68	77	structure	evidence	The TTD is coloured in green and the Spacer in yellow in TTD–Spacer structure.	FIG
0	15	TTD–PHD–H3K9me3	complex_assembly	TTD–PHD–H3K9me3 complex is coloured in grey, and the PHD and H3K9me3 are omitted for simplicity.	FIG
53	56	PHD	structure_element	TTD–PHD–H3K9me3 complex is coloured in grey, and the PHD and H3K9me3 are omitted for simplicity.	FIG
61	63	H3	protein_type	TTD–PHD–H3K9me3 complex is coloured in grey, and the PHD and H3K9me3 are omitted for simplicity.	FIG
63	68	K9me3	ptm	TTD–PHD–H3K9me3 complex is coloured in grey, and the PHD and H3K9me3 are omitted for simplicity.	FIG
58	61	TTD	structure_element	(c) Electrostatic potential surface representation of the TTD with the Spacer shown in ribbon representation.	FIG
71	77	Spacer	structure_element	(c) Electrostatic potential surface representation of the TTD with the Spacer shown in ribbon representation.	FIG
29	35	Spacer	structure_element	The critical residues on the Spacer for the interaction are shown in stick representation.	FIG
21	31	TTD–Spacer	structure_element	(d) Close-up view of TTD–Spacer interaction.	FIG
0	14	Hydrogen bonds	bond_interaction	Hydrogen bonds are indicated as dashed lines.	FIG
19	22	ITC	experimental_method	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
23	37	enthalpy plots	evidence	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
70	76	Spacer	structure_element	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
85	88	TTD	structure_element	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
93	100	TTD–PHD	structure_element	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
121	137	binding affinity	evidence	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
139	141	KD	evidence	(e–g) Superimposed ITC enthalpy plots for the interaction between the Spacer and the TTD (or TTD–PHD) with the estimated binding affinity (KD) indicated.	FIG
0	9	Wild-type	protein_state	Wild-type and mutant proteins for the measurements are indicated.	FIG
14	20	mutant	protein_state	Wild-type and mutant proteins for the measurements are indicated.	FIG
4	24	GST pull-down assays	experimental_method	(h) GST pull-down assays for the intramolecular interactions.	FIG
4	13	wild-type	protein_state	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
42	47	UHRF1	protein	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
68	78	GST-tagged	protein_state	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
79	82	TTD	structure_element	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
84	90	Linker	structure_element	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
94	100	Spacer	structure_element	The wild-type or indicated truncations of UHRF1 were incubated with GST-tagged TTD, Linker or Spacer.	FIG
0	6	Hm-DNA	chemical	Hm-DNA impairs the intramolecular interaction of UHRF1 and facilitates its histone recognition.	FIG
49	54	UHRF1	protein	Hm-DNA impairs the intramolecular interaction of UHRF1 and facilitates its histone recognition.	FIG
75	82	histone	protein_type	Hm-DNA impairs the intramolecular interaction of UHRF1 and facilitates its histone recognition.	FIG
4	10	Hm-DNA	chemical	(a) Hm-DNA impairs the intramolecular interaction of PHD–SRA.	FIG
53	60	PHD–SRA	structure_element	(a) Hm-DNA impairs the intramolecular interaction of PHD–SRA.	FIG
4	7	SRA	structure_element	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
12	21	incubated	experimental_method	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
27	37	GST-tagged	protein_state	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
38	41	PHD	structure_element	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
49	60	presence of	protein_state	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
90	96	hm-DNA	chemical	The SRA was incubated with GST-tagged PHD in the presence of increasing concentrations of hm-DNA and immobilized on glutathione resin.	FIG
36	44	SDS–PAGE	experimental_method	The bound proteins were analysed in SDS–PAGE and Coomassie blue staining (left) and quantified by band densitometry (right).	FIG
49	72	Coomassie blue staining	experimental_method	The bound proteins were analysed in SDS–PAGE and Coomassie blue staining (left) and quantified by band densitometry (right).	FIG
98	115	band densitometry	experimental_method	The bound proteins were analysed in SDS–PAGE and Coomassie blue staining (left) and quantified by band densitometry (right).	FIG
26	31	UHRF1	protein	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
49	64	histone peptide	experimental_method	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
66	68	H3	protein_type	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
68	73	K9me0	ptm	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
75	90	pull-down assay	experimental_method	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
120	126	Hm-DNA	chemical	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
169	179	TTD–Spacer	structure_element	(b) Purified fragments of UHRF1 were analysed by histone peptide (H3K9me0) pull-down assay as described in Fig. 1b. (c) Hm-DNA impairs the intramolecular interaction of TTD–Spacer.	FIG
0	10	SRA–Spacer	structure_element	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
15	24	incubated	experimental_method	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
30	40	GST-tagged	protein_state	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
41	48	TTD–PHD	structure_element	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
52	55	TTD	structure_element	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
63	74	presence of	protein_state	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
104	110	hm-DNA	chemical	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
127	147	pull-down experiment	experimental_method	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
182	201	band densitometries	experimental_method	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
226	249	Coomassie blue staining	experimental_method	SRA–Spacer was incubated with GST-tagged TTD–PHD or TTD in the presence of increasing concentrations of hm-DNA and analysed in pull-down experiment as described in a. The quantified band densitometries are indicated below the Coomassie blue staining.	FIG
4	35	Histone peptide pull-down assay	experimental_method	(d) Histone peptide pull-down assay using UHRF1 mutants as indicated.	FIG
42	47	UHRF1	protein	(d) Histone peptide pull-down assay using UHRF1 mutants as indicated.	FIG
48	55	mutants	protein_state	(d) Histone peptide pull-down assay using UHRF1 mutants as indicated.	FIG
44	47	DTT	chemical	The assays were performed in the presence (+DTT) or absence (−DTT) of 15 mM DTT.	FIG
62	65	DTT	chemical	The assays were performed in the presence (+DTT) or absence (−DTT) of 15 mM DTT.	FIG
76	79	DTT	chemical	The assays were performed in the presence (+DTT) or absence (−DTT) of 15 mM DTT.	FIG
4	10	Spacer	structure_element	The Spacer facilitates hm-DNA–SRA interaction and DNMT1–UHRF1 interaction.	FIG
23	29	hm-DNA	chemical	The Spacer facilitates hm-DNA–SRA interaction and DNMT1–UHRF1 interaction.	FIG
30	33	SRA	structure_element	The Spacer facilitates hm-DNA–SRA interaction and DNMT1–UHRF1 interaction.	FIG
50	61	DNMT1–UHRF1	complex_assembly	The Spacer facilitates hm-DNA–SRA interaction and DNMT1–UHRF1 interaction.	FIG
17	20	ITC	experimental_method	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
21	35	enthalpy plots	evidence	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
40	65	hm-DNA-binding affinities	evidence	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
73	76	SRA	structure_element	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
82	88	Spacer	structure_element	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
93	103	SRA–Spacer	structure_element	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
124	160	fluorescence polarization (FP) plots	evidence	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
165	190	hm-DNA-binding affinities	evidence	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
209	220	full-length	protein_state	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
221	226	UHRF1	protein	(a) Superimposed ITC enthalpy plots for hm-DNA-binding affinities of the SRA, the Spacer and SRA–Spacer. (b,c) Superimposed fluorescence polarization (FP) plots for hm-DNA-binding affinities of truncations or full-length UHRF1.	FIG
14	32	binding affinities	evidence	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
34	36	KD	evidence	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
88	98	GFP-tagged	protein_state	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
99	108	wild-type	protein_state	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
122	129	mutants	protein_state	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
133	138	UHRF1	protein	The estimated binding affinities (KD) are listed above. (d) Subcellular localization of GFP-tagged wild-type or indicated mutants of UHRF1 in NIH3T3 cells.	FIG
54	58	DAPI	chemical	The percentages of cells showing co-localization with DAPI foci were counted from at least 100 cells and shown on the left of the corresponding representative confocal microscopy.	FIG
159	178	confocal microscopy	experimental_method	The percentages of cells showing co-localization with DAPI foci were counted from at least 100 cells and shown on the left of the corresponding representative confocal microscopy.	FIG
21	45	GST pull-down experiment	experimental_method	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
75	84	wild-type	protein_state	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
88	99	truncations	experimental_method	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
103	108	UHRF1	protein	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
113	122	RFTSDNMT1	protein	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
170	176	hm-DNA	chemical	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG
212	217	UHRF1	protein	Scale bar, 5 μm. (e) GST pull-down experiment for the interactions between wild-type or truncations of UHRF1 and RFTSDNMT1 as described in Fig. 2a. (f) Working model for hm-DNA-mediated conformational changes of UHRF1, as described in the Discussion.	FIG