Protein: Chromodomain Y-like protein (CDY-like) (Crotonyl-CoA hydratase) (EC 4.2.1.-) (Q9Y232)
Organism: Homo sapiens (Human)
Function: Chromatin reader protein that recognizes and binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively). Part of multimeric repressive chromatin complexes, where it is required for transmission and restoration of repressive histone marks, thereby preserving the epigenetic landscape. Required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes. Acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression. Involved in X chromosome inactivation in females: recruited to Xist RNA-coated X chromosome and facilitates propagation of H3K9me2 by anchoring EHMT2 (By similarity). Promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), thereby facilitating transcriptional repression at sites of DNA damage and homology-directed repair of DSBs. Required for neuronal migration during brain development by repressing expression of RHOA (By similarity). By repressing the expression of SCN8A, contributes to the inhibition of intrinsic neuronal excitability and epileptogenesis (By similarity). In addition to acting as a chromatin reader, acts as a hydro-lyase. Shows crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone crotonylation. Histone crotonylation is required during spermatogenesis; down-regulation of histone crotonylation by CDYL regulates the reactivation of sex chromosome-linked genes in round spermatids and histone replacement in elongating spermatids (By similarity). By regulating histone crotonylation and trimethylation of H3K27, may be involved in stress-induced depression-like behaviors, possibly by regulating VGF expression (By similarity).
Subcellular location: [Isoform 2]: Nucleus {ECO:0000269|PubMed:18450745, ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:29177481}. Chromosome {ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:29177481}. Note=Recognizes and binds histone H3 trimethylated at 'Lys-9', dimethylated at 'Lys-27' and trimethylated at 'Lys-27' (H3K9me3, H3K27me2 and H3K27me3, respectively) on chromatin (PubMed:19808672). Multimerization is required for chromatin-binding (PubMed:19808672). Recruited to sites of DNA double strand breaks in a PARP1-dependent fashion (PubMed:29177481). {ECO:0000269|PubMed:19808672, ECO:0000269|PubMed:29177481}.
Interaction partners:
- Histone-lysine N-methyltransferase EHMT2
- Mesoderm induction early response protein 1
- Protein Wiz
- Histone-lysine N-methyltransferase EHMT1
- Histone-lysine N-methyltransferase EZH2
- Histone deacetylase 1
- Histone-lysine N-methyltransferase SETDB1
- Histone deacetylase 2
- Sterol carrier protein 2
- Hydroxysteroid dehydrogenase-like protein 2
Sequence:
MTFQASHRSAWGKSRKKNWQYEGPTQKLFLKRNNVSAPDGPSDPSISVSSEQSGAQQPPALQVERIVDKRKNKKGKTEYLVRWKGYDSEDDTWEPEQHLVNCEEYIHDFNRRHTEKQKESTLTRTNRTSPNNARKQISRSTNSNFSKTSPKALVIGKDHESKNSQLFAASQKFRKNTAPSLSSRKNMDLAKSGIKILVPKSPVKSRTAVDGFQSESPEKLDPVEQGQEDTVAPEVAAEKPVGALLGPGAERARMGSRPRIHPLVPQVPGPVTAAMATGLAVNGKGTSPFMDALTANGTTNIQTSVTGVTASKRKFIDDRRDQPFDKRLRFSVRQTESAYRYRDIVVRKQDGFTHILLSTKSSENNSLNPEVMREVQSALSTAAADDSKLVLLSAVGSVFCCGLDFIYFIRRLTDDRKRESTKMAEAIRNFVNTFIQFKKPIIVAVNGPAIGLGASILPLCDVVWANEKAWFQTPYTTFGQSPDGCSTVMFPKIMGGASANEMLLSGRKLTAQEACGKGLVSQVFWPGTFTQEVMVRIKELASCNPVVLEESKALVRCNMKMELEQANERECEVLKKIWGSAQGMDSMLKYLQRKIDEF