   ª²8!&CÊÐ³¹¼7ärw¯­6õÈÒS_cNK`ZSd\RdP9¥ÇuÙ©HaL`O\ƼÞÙơƝŷįƣØßŁÂőßŎŗő¨ÛƆ¬õß¨Ƨ   ƣèç³²Ňæƕ¨Ń
Tissue specific transcriptional regulation in plants
and time series analysis tool for single cell data
Keyword: transcriptional regulation, cis-element, circadian clock, tissue specificity, single
cell transcriptome
Kotaro tori & Motomu Endo
Graduate School of Biostudies, Kyoto University
Kitashirakawa-oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
DOI: 10.24480/bsj-review.8b5.00115
õ

 9ärw8!&CMNèu9éÖģĺƠÛ6ħŴIƞ©5ņċ'E+?57ƞ©4ƠÛņľ¬õöƵ1EƠÛņľ¬õ6ƚœ57Ə¦ÆÛ5BEƏ¦¬õ6<5RNaseA~miRNA~f}]}[ÔńÝ mRNA ¨ſħĥ435BE RNA 6¨ſu_z±AÐÎ6¥ĥĀ5BE RNA
ƹDNA Al[d}6ƹ5žCFEQmZPibM`S4¬õ436×6¬õīƮÝË%0E"%+×Ħ4¬õīƮ6

1@Ə¦ÆÛ5BEƏ¦¬õ7 RNA 6ħ

Ŵņľ50ė@ÎĜň/ƦŽ4¬õīƮ1EvczģĺY|Nhf\f17Š2,000 6Ə¦ÆÛÝË%)FC7Y[Ƥª2Á8FEĎÐÎC4v_nƤª5ťº'E"21Ħ4Ə¦¬õIŸ.0E2űCF0EƾVandepoele et al. 2009ƿŒ°14ģĺ7¿È6ŀÑÔ±5Ʃč5÷Ś'EöŽE+?¢~Ĵî~Į
¨~Ð~ƚƥ±ĺ436ŀÑ­ķ5÷Ś'E+?6Ļńň4Y[ƤªIņƛ$(0+¢÷Śú6ƠÛ7o|v^5 G-boxƾCACGTGƿ2Á8FEY[ƤªIć/"2Ō
CF0DY|Nhf\f6Š 3ƽ6ƠÛo|v^ƶÍ5 G-box Ić.0EƾMichael and McClung 2003ƿƾÉ 1ƿ=+Ĵ­ķAĹ­ķ~Ð[d{[6÷Ś5ƭH
EY[Ƥª2%0 C-repeat (CRT)/drought-responsive element (DRE)ƾA/GCCGACƿƻĴ:
6÷Ś5HEY[Ƥª2%0 HS-1ƾATGGGCCCTAƿA HS-2(GTT(A/C)TAGA)ƚƥ±ĺ6÷Ś5HEY[Ƥª2%0 ROS-1ƾ(TA)4G(AT)4ƿA ROS-2ƾTTCAATTTƿÏ¾$F0EƾRushton et al. 2002, Geisler et al. 2006ƿ"%+ŀÑÔ±6÷Ś5ƭHEY[Ƥ $%""  # $  %!&"!'      ª6-ė@íŜ4ƠÛņľ¬õ5ƭH.0E@67Ĥđy\t¬õ5ƭHEY[Ƥª1Eá5
Y|Nhf\f6 89ƽ6ƠÛ7ĒĖĞ1Š 24 ĔƬ¿Ě6
ņľĉ°IŐ%0E(Michael et al.
2008, Endo et al. 2014)"6ņľĉ°57¢­ķ5BEņľ¬õ@½=
F0E@66¢÷Śú6ƠÛ
7¤ƠÛ6Š 19ƽ1E"2
CØƢ¨6ƠÛ6ņľĉ°7Ĥ
đĔƀ5BE@6,2űCF0EƾJiao et al. 2005ƿģĺ6ĤđĔƀIĥĀ'EĔƀƠÛ7Ə¦ÆÛIVe%0DęĐ5ņľmSIć/
CIRCADIAN CLOCK ASSOCIATED 1(CCA1)2 LATE ELONGATED  MbJVUOU8!4·Ä8""
ECMNèuFZb]dPd8>çm9y~

HYPOCOTYL (LHY)7evening
element (EE; AAAATATCT)2Á8FEY[ƤªIƂƇ'EƾÉ 2ƿ5@ EE 5Ƹ%+
CCA1-binding site (CBS; AAAAATCT)@Ï¾$F0D"FC7)F*F¤ƠÛ6 25ƽ
B9 35ƽ6o|v^ƶÍ5ÝË%0EƾWang et al. 1997, Harmer et al. 2000, Michaeland McClung 2003)CCA1/LHY 7ēƴ5ņľmSIć/ PSEUDO RESPONSE
REGULATOR 9 (PRRǁ)/ PRR7/ PRR5 ƠÛŰ436ĔƀƠÛ6Ə¦I'2»Ĕ5ÕĐ
5ņľmSIć/ TIMING OF CAB EXPRESSION 1 (TOC1)LUX ARRHYTHMO (LUX)
EARLY FROWERING 4 (ELF4)436ņľIă¬'ETOC1 7 TOC1 morning elementƾT1ME;TGTGƿ2Á8FEY[ƤªIƂƇ%LUX 7 LUX binding site (LBS; GAT(A/T)CG)2Á8F
EY[ƤªIƂƇ'E(Chow et al. 2012, Gendron et al. 2012)"FC6ĤđĔƀ^}kSƈ5
ƂƇ$FEY[7ƤªI¤0ºH(E2¡5Ɣ;+B5¤ƠÛ64D6Ƣ¨7ĤđĔƀ¬õ1E2ü$FE $%""  # $  %!&"!'       ô¬¢¥ÚF­,C¥Úçmë9ärYIdTWQK
j:PcXKÞØ:çmF¿*ñ5Õ)D4C9:¡"A8"&4º¶,C¥Úçm5B»:£&¡"A¤8"&4º¶,C¥ÚçmF¿*4Cçm9g8:.D/D9¥Úçm8<DCMNèuF¿*4C±Î:çm9ÑÛF*Î:çm9ärwFÕ*4Cö ärw¯­9ÊÐ³¹"%+Ĥđy\t¬õ5ƭHEY[Ƥª75ģĺ¤6ſğCĒC5$F+@61E%%Y[Ƥª5BEƏ¦¬õ57ţŭĻńúÝË'E"2Ɠë6ţ
ŭ{pz6dx}[SyodtſğCĒC5$F//Eŧśĝ1Ĥđy\tIŐ'ƠÛ6o|v^ƶÍ57long-day vasculature element (LVEǂ ACACGG)A shortday vasculature element (SVEǂ GCGGGA)2.+ď%Y[Ƥªž§$F0D"F
CIć/ƠÛ7ŶŲ436ţŭ17Ĥđy\tIŐ$4$C5telo-boxƾTBXƿ
A starch boxƾSBXƿprotein boxƾPBXƿ2.+Y[ƤªI@/ƠÛ75ŶŲ5EĤđy\t5ƭH.0Dŧśĝ16Ĥđy\tðĀ57ƭHC42űCFEƾMichael et al. 2008, Endo et al. 2014ƿ"6B4ţŭ#25Ļńň4Y[Ƥª6ÝË7
)FIƂƇ'EƏ¦ÆÛ=+7ħŴ5ţŭĻńúE+?,2űCFEáƯĔƀƠÛ ELF4 7ŧśĝ1Ļ5ƻņľIć.0E"2Ő$F0Dpromoter::GUS {q^6áƺC7 PRR3 A PRRǁ@=+ŧśĝ1ƻņľIć.0E"2ŐÄ$F0
 $%""  # $  %!&"!'      EƾPara et al. 2007, Endo et al. 2014ƿ"6B4ţŭĻńň4ĔƀƠÛ6ņľB9ţ
ŭĻńň4Y[Ƥª6ÝË7ţŭ#25ń4EĤđĔƀ6ħŴIýÀ%0D"F=1
5ġ~ÌƢ~ĭÜ~źŉ~ŧśĝ16Ļńň4Ĥđy\tÝË'E"2Ő$F0EƾThain et al. 2002, Yarik et al. 2011, Endo et al. 2014ƿ"%+ţŭĻńň4Y[ƤªAţŭĻńň4ĔƀƠÛ6ņľ7YwOZwOjQAr
O[ld431@)6ÝËŌCF0DŁĺŕIƊ+ĕƙň4ţ>1E2űCFEƾSmith et al. 2007, Kalay and Wittkopp 2010ƿ=+ĤđĔƀ65@ģĺ6ţŭĻńň4Ə¦¬õ62%0ŵƸ6ÿĠ5â'EƏ¦¬õ»6ƠÛ1.0@ţŭ#2
5¤ń4DƏ¦¬õ6yo|Txs}TţŭĻńň5ŸHFE"2ŌCF0EƾLyons et al. 2015ƿ$C5šÖŪ~ĳƖÊ~Ĺ~Ĵ~ƻĴ~436[d{[@ţŭ#25ń4EƠÛņľIƃã'E"2ŌCF0D×Ħ4[d{[÷Ś50@ţŭĻńň4Y[Ƥª6ÝËűCF0EƾSwindell et al. 2007, Singh et al. 2015ƿ÷  ÈÒÙ©
"6B5ØƢ¨6ƠÛ6Ə¦¬õ5ƭHEĤđy\tI7&?×ŁĿ÷Śţŭ#25ń4EƏ¦¬õIŸ.0E"27Ə¦¬õ6ſğ57ţŭAŢų6ƜI³«%
0ŸH4

F84C4"2IýÀ'E=+Ɠë6ſğC»2ùHF0+Ţųń4EħŴI@.0EU[AŢų57úE"2ŋĩ1Ő$F0E"2
CŁÂ6ÎĜµ1EŢų{pz6ņľſğIŸ"21BD×Ħ1Şū4Ə¦¬õ
uRg\tĒC54E2Ěò$F0Eì5@Ɠë6ĂŹƘĪ5BDģĺ1@ 1
Ţų{pz1dx}[SyodtſğIŸ"2¸Ŵ54.00EƾEfroni et al.
2016ƿ)6ĂŹň4ƁŢ5/07'15BSJ-Review vol. 7 61Ŕ¶Ó5BDƁ%ſƄ$F0E+?ƾ 2016ƿĜŖ17¯þ%""17 1 Ţų RNA sequencing
5BDôCF+ƠÛņľc^6Ĕşªſğāı5/0ƄĒ'E
"F=1ž0+B5Ə¦¬õ2Ĥđy\t7¸¨1E+?6Ţų1ƠÛņľIĵà'EƯ57EĔĸ6ņľIžE,17´¨1DĔşªſğIŸ"

21ƠÛņľ6y\tIƀĵ'EöŽE%%ľË6 1 ŢųſğĻ5dx}[
Syodtſğ17ŢųIŏÒ%0 RNA IĆ§%0E+?»6ŢųCĔşªc^IôE"27·Ŀ¸Ŵ1E"%+ÅƷIſİ'E+?żĎ6ŢųCô+ƠÛņľc^I/4ºH(Ņň4Ĕşªc^I¥ĥĀ'EāıűĢ$F0
E)61źň4LzWy\t1E MonocleƾTrapnell et al. 2014ƿ7ĽřĀ¨¨ğ5BDƠÛņľc^6ĩÊŬIŸ2 ĩêƳ5Ąñ$F+¹Ţų5â%ėä¤ÍěƾMSTƿIł0¹ĸI/4ƒ6ũÃėō24EŤƍIĊ%§'ĩ5ŢųI/4 MST 6ƪ$ėƪ24EŤƍIŢų¨±64Ǝƌ2%0ĔşªIĥŝ'ELzW
y\t1EƾÉ 3ƿ"6B5ƠÛņľc^CŢųƬ6ƋƱƾņľo|nKNz6ƸîƿI@25ŢųÔ±6ĔşªI¥ĥŝ'E"21Čň4ĔƬƐƾpseudotimeƿIĀ'E"21EľË17pseudo-time I¥ĥŝ'EĦ4LzWy\t
Ï¾$F0DſğŊň5÷&0Ɵą1Eƾź 1ƿ $%""  # $  %!&"!'      RdP

°oÏ8@14}ÈÒ9³:ïf8Õ¶)DC

ÈÒë8¦p ¨ò óF­Æ,C

PJZ8+4ÈÒ
F_[a,C
Fl*4 
f8ÈÒFh;CÈÒ9çmº¶#
°oÂëq8Õ)DCçm  9º¶XPdc



 F¥ëå6*4}çm9º¶XPdcF¾Ü5$C  8@C¥ÇuÙ©9¬Ö 8¸Cçmº¶RdP:õçmFõ°o6=7,ð°o^dK`QTÂëq5Õ)D4C5:n¼8e°oÂë59}ÈÒ9º¶ZbYGJaF¿*4
C :(9@7RdPF¸4´Ãtt©8@C°oÏFÔ°of59çmº¶F|Ó7ìBÍ*0<<}ÈÒ9º¶ZbYGJaF  °of8Õ,°8¦p¨òó8@B}±F27%ËâF­Æ*.9i5à

í#¦ê67CËâFÈÒtz9ãá6*4æ,C(9ãáFkå6*4ÈÒt
z9¥xFÅs*Ì4(9kå"AíD0ãá8CÈÒ9¥xF×Á?
Bkåf827'¥xF)-C5:ß½{5ÈÒtz9¦v§8CÈÒî½{5¦?§8CÈÒF¿*4C.9³¼7çmº¶F?68}ÈÒ9®ÝFÔAD0RdP:ÈÒÀ8+4³¹¼8º¶,Cçm9«s f59çmº¶XPdc9Ù©}K_NPdF³3&Cçm98¸C(6#5$C $%""  # $  %!&"!'      Õ  

 8!&Ck7¥ÇuÙ©HaL`O\ź 1 5Ĉ!+<2J36LzWy\t7Txn1¹ĸ6ƋƱIėō5'E"21
pseudo-time IĀ'E"FC6āı27ń4Eņü1ĔƬƐIĀ'ELzWy\t@ÝË'EOscopeƾLeng et al. 2015ƿ7Ʋ»ƅň5Ţų¨ŻIŸŢųưÇCô+ 1 Ţų RNA seq c^CŢų¨Ż6XNSz6
1E$C5Ţų¨Ż6XNSz6

1ņľĉ°'EƠÛIĊ%§'"2

16X}oz36Ĕĸ5Ů'E6ņľĉ°IŸƠÛ6ņľƨ5ĲŊ'E"21Ļà%Ţų¨Ż¿ĚIĔƬƐ2'EĔşªc^Iĥŝ'Eó7 Oscope 5Ŧ×Ħ4·Ŀ1ĔşªIĥŝ'ELzWy\t6ƫņĘ=F0DĻ56áƺş26ĬƑIŸ5+?57áƯ6ĔƬ[Uz2â÷¸Ŵ4ĔşªſğöƵ1E"F5BD1 Ţų{pz16Ĕşªſğ¸Ŵ24
DŢų^NoĻńň5ħŴ'EƏ¦ÆÛAY[ƤªIž§%Ţų{pz6Ə¦¬õħĥIĒC51E2Ěò1Eø ÉEB8
ĤđĔƀ5BEŨůň4Ə¦¬õ7ØƢ¨6ƠÛņľ5đ¿Ô°IïƉ"'+?Ə¦¬õIĿſ'E1ĔƬ2Ĥø7Ʋé5ƦŽ1E$C5ĤđĔƀI½?
/6Ə¦¬õ7ţŭ#25ń4.0E"2CţŭAŢų6B4ŘƬûÏ@Ə $%""  # $  %!&"!'      ¦¬õIĿſ'E1Ĩ(4"%+"2Có7BDƻĔŘƬſî16Ə¦ſğį?CF0EǀŢųdx}[SyodtſğA pseudo-time p[6Ĕşªſğ7"%+g\IĶ+'ĩ6ĂŹ1Dó='='ƦŽ4az24E,G"FC6ĂŹ7'15ģĺ1@ã£$FÚ?0D"%+ſğIƗ&0ĔŘƬ
Ļńň4ď+4Ə¦¬õuRg\tIņž~Ŀſ1E2Ěò$FE

ù ¸

µ

Bendall, S.C., Davis, K.L., Amir, el-AD., Tadmor, M.D., Simonds, E.F., Chen, T.J., Shenfeld, D.K.,
Nolan, G.P., Pe’er, D. 2014. Single-cell trajectory detection uncovers progression and regulatory
coordination in human B cell development. Cell. 157: 714–725.
Chow, B.Y., Helfer, A., Nusinow, D.A., Kay, S.A. 2012. ELF3 recruitment to the PRR9 promoter
requires other Evening Complex members in the Arabidopsis circadian clock. Plant Signal.
Behav. 7: 170–173.
Efroni, I., Mello, A., Nawy, T., Ip, P.L., Rahni, R., DelRose, N., Powers, A., Satija, R., Birnbaum,
K.D., Birnbaum, K.D. 2016. Root regeneration triggers an embryolike sequence guided byhormonal interactions. Cell. 165: 1721–1733.
Endo, M., Shimizu, H., Nohales, M.A., Araki, T., Kay, S.A. 2014. Tissue-specific clocks in
Arabidopsis show asymmetric coupling. Nature. 515: 419–422.
Geisler, M., Kleczkowski, L.A., Karpinski, S. 2006. A universal algorithm for genome-wide insilicio identification of biologically significant gene promoter putative cis-regulatory-elements;
identification of new elements for reactive oxygen species and sucrose signaling in
Arabidopsis. Plant J. 45: 384–398.
Gendron, J.M., Pruneda-Paz, J.L., Doherty, C.J., Gross, A.M., Kang, S.E., Kay, S.A.
2012. Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor. Proc
Natl Acad Sci USA. 109: 3167–3172.
Harmer, S. L., Hogenesch, J. B., Straume, M., Chang, H.S., Han, B., Zhu, T., Wang, X., Kreps, J.A.,
Kay, S.A. 2000. Orchestrated transcription of key pathways in Arabidopsis by the circadianclock. Science. 290: 2010–2013.
Ji, Z., Ji, H. 2016. TSCAN: Pseudo Time Reconstruction and Evaluation in Single-cell RNA-seq
Analysis. Nucleic Acids Research. 44: e117.
Jiao, Y., Ma, L., Strickland, E., Deng, X.W. 2005. Conservation and divergence of light-regulated
genome expression patterns during seedling development in rice and Arabidopsis. Plant
Cell. 17: 3239–3256.
Julia, M., Telenti, A., Rausell, A. 2015. Sincell: an R/Bioconductor package for statistical assessmentof cell-state hierarchies from single-cell RNA-seq. Bioinformatics. 31: 3377–3379.
Kalay, G., Wittkopp, P.J. 2010. Nomadic enhancers: tissue-specific cis-regulatory elements of yellow
have divergent genomic positions among Drosophila species. PLoS Genet. 6: e1001222.
Ŕ ĩYU}XIł+ŢųƠÛņľſğ6ľļ2åĘģĺŢų
6yo|Txs}Tħĥ6ſĒ5¼

0ģĺőß6ė®Ū  $%""  # $  %!&"!'      

Leng, N., Chu, L., Barry, C., Li, Y., Choi, J., Li, X., Jiang, P., Stewart, R.M., Thomson, J.A.,
Kendziorski, C. 2015. Oscope identifies oscillatory genes in unsynchronized single-cell RNAseq experiments. Nature methods. 12: 947–950.
Lyons, R., Stiller, J., Powell, J., Rusu, A., Manners, J. M., Kazan, K. 2015. Fusarium
oxysporum triggers tissue-specific transcriptional reprogramming in Arabidopsis thaliana. PLoS
ONE. 10: e0121902.
Michael, T.P., Mockler, T.C., Breton, G., McEntee, C., Byer A., Trout, J.D., Hazen, S.P., Shen, R.,
Priest, H.D., Sullivan, C.M., Givan, S.A., Yanovsky, M., Hong, F., Kay, S.A., Chory, J. 2008.
Network discovery pipeline elucidates conserved time-of-day-specific cis-regulatory modules.
PLoS Genet. 4: e14.
Michael, T.P., McClung, C.R. 2003. Enhancer trapping reveals widespread circadian clocktranscriptional control in Arabidopsis. Plant Physiol. 132: 629–639.
Para, A., Farre, E.M., Imaizumi, T., Pruneda-Paz, J.L., Harmon, F.G., Kay, S.A. 2007. PRR3 is avascular regulator of TOC1 stability in the Arabidopsis circadian clock. Plant Cell. 19: 3462–
3473.
Rushton, P.J., Reinstadler, A., Lipka, V., Lippok, B., Somssich, I.E. 2002. Synthetic plant promoters
containing defined regulatory elements provide novel insights into pathogen- andwoundinduced signaling. Plant Cell. 14: 749–762.
Setty, M., Tadmor, M.D., Reich-Zeliger, S., Angel, O., Salame, T.M., Kathail, P., Choi, K., Bendall,S.C., Friedman, N., Pe'er, D. 2016. Wishbone identifies bifurcating developmental trajectories
from single-cell data. Nature Biotechnol. 34: 637–645.
Shin, J., Berg, D.A., Zhu, Y., Shin, J.Y., Song, J., Bonaguidi, M.A., Enikolopov, G., Nauen, D.W.,
Christian, K.M., Ming, G.L., Song, H. 2015. Single-cell RNA-Seq with waterfall reveals
molecular cascades underlying adult neurogenesis . Cell Stem Cell. 17: 360 –372.
Singh, A., Kushwaha, H.R., Soni, P., Gupta, H., Singla-Pareek, S.L., Pareek, A. 2015. Tissue specificand abiotic stress regulated transcription of histidine kinases in plants is also influenced by
diurnal rhythm. Front. Plant Sci. 6: 711.
Smith, A.D., Sumazin, P., Zhang, M. Q. 2007. Tissue-specific regulatory elements in mammalianpromoters. Mol syst Bio. 3: 73.
Swindell, W.R., Huebner, M., Weber, A.P. 2007. Transcriptional profiling of Arabidopsis heat shockproteins and transcription factors reveals extensive overlap between heat and non-heat stressresponse pathways. BMC Genomics. 8: 125.
Thain, S.C., Murtas, G., Lynn, J.R., McGrath, R.B., Millar, A.J. 2002. The circadian clock that
controls gene expression in Arabidopsis is tissue specific. Plant Physiology. 130: 102–110.
Trapnell, C., Cacchiarelli, D., Grimsby, J., Pokharel, P., Li, S., Morse, M., Lennon, N.J., Livak, K.J.,
Mikkelsen, T.S.,, Rinn, J.L. 2014. The dynamics and regulators of cell fate decisions are
revealed by pseudotemporal ordering of single cells. Nat. Biotechnol. 32: 381–386.
Vandepoele, K., Quimbaya, M., Casneuf, T., De Veylder L., Van de Peer Y. 2009. Unravelingtranscriptional control in Arabidopsis using cis-regulatory elements and coexpression
networks. Plant Physiol. 150: 535–546

 $%""  # $  %!&"!'      

Wang, Z.Y., Kenigsbuch, D., Sun, L., Harel, E., Ong, M.S., Tobin, E.M. 1997. A Myb-relatedtranscription factor is involved in the phytochrome regulation of an Arabidopsis Lhcb
gene. Plant Cell. 9: 491–507.
Welch, J. D., Hartemink A. J., Prins J. F. 2016. SLICER: inferring branched, nonlinear cellular
trajectories from single cell RNA-seq data. Genome Biol. 17: 106.
Yakir, E., Hassidim, M., Melamed-Book, N., Hilman, D., Kron, I., Green, R.M. 2011. Cell
autonomous and cell-type specific circadian rhythms in Arabidopsis. Plant J. 68: 520–31.

 $%""  # $  %!&"!'   