Mediator and cohesin connect gene expression and chromatin architecture

被引:1427
作者
Kagey, Michael H. [1 ]
Newman, Jamie J. [1 ,2 ]
Bilodeau, Steve [1 ]
Zhan, Ye [3 ,4 ]
Orlando, David A. [1 ]
van Berkum, Nynke L. [3 ,4 ]
Ebmeier, Christopher C. [5 ]
Goossens, Jesse [5 ]
Rahl, Peter B. [1 ]
Levine, Stuart S. [2 ]
Taatjes, Dylan J. [5 ]
Dekker, Job [3 ,4 ]
Young, Richard A. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA
[4] Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA
[5] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA
基金
加拿大健康研究院;
关键词
EMBRYONIC STEM-CELLS; DE-LANGE-SYNDROME; TRANSCRIPTIONAL REGULATORY CIRCUITRY; INTEGRATION HOST FACTOR; NIPPED-B; COACTIVATOR; ACTIVATION; PROTEINS; COMPLEX; MED12;
D O I
10.1038/nature09380
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Transcription factors control cell-specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. Here we report that mediator and cohesin physically and functionally connect the enhancers and core promoters of active genes in murine embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with cohesin, which can form rings that connect two DNA segments. The cohesin-loading factor Nipbl is associated with mediator-cohesin complexes, providing a means to load cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by mediator and cohesin. Mediator and cohesin co-occupy different promoters in different cells, thus generating cell-type-specific DNA loops linked to the gene expression program of each cell.
引用
收藏
页码:430 / 435
页数:6
相关论文
共 50 条
[1]  
ADHYA S, 1989, ANNU REV GENET, V23, P227, DOI 10.1146/annurev.genet.23.1.227
[2]   Cohesinopathies, gene expression, and chromatin organization [J].
Bose, Tania ;
Gerton, Jennifer L. .
JOURNAL OF CELL BIOLOGY, 2010, 189 (02) :201-210
[3]   Core transcriptional regulatory circuitry in human embryonic stem cells [J].
Boyer, LA ;
Lee, TI ;
Cole, MF ;
Johnstone, SE ;
Levine, SS ;
Zucker, JR ;
Guenther, MG ;
Kumar, RM ;
Murray, HL ;
Jenner, RG ;
Gifford, DK ;
Melton, DA ;
Jaenisch, R ;
Young, RA .
CELL, 2005, 122 (06) :947-956
[4]   Looping versus linking: toward a model for long-distance gene activation [J].
Bulger, M ;
Groudine, M .
GENES & DEVELOPMENT, 1999, 13 (19) :2465-2477
[5]   Enhancers: The abundance and function of regulatory sequences beyond promoters [J].
Bulger, Michael ;
Groudine, Mark .
DEVELOPMENTAL BIOLOGY, 2010, 339 (02) :250-257
[6]   ROLE OF INTEGRATION HOST FACTOR IN THE REGULATION OF THE GLNHP2 PROMOTER OF ESCHERICHIA-COLI [J].
CLAVERIEMARTIN, F ;
MAGASANIK, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (05) :1631-1635
[7]   The mammalian Mediator complex and its role in transcriptional regulation [J].
Conaway, RC ;
Sato, S ;
Tomomori-Sato, C ;
Yao, TT ;
Conaway, JW .
TRENDS IN BIOCHEMICAL SCIENCES, 2005, 30 (05) :250-255
[8]   Capturing chromosome conformation [J].
Dekker, J ;
Rippe, K ;
Dekker, M ;
Kleckner, N .
SCIENCE, 2002, 295 (5558) :1306-1311
[9]   Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation [J].
Ding, Ning ;
Zhou, Haiying ;
Esteve, Pierre-Olivier ;
Chin, Hang Gyeong ;
Kim, Seokjoong ;
Xu, Xuan ;
Joseph, Sumy M. ;
Friez, Michael J. ;
Schwartz, Charles E. ;
Pradhan, Sriharsa ;
Boyer, Thomas G. .
MOLECULAR CELL, 2008, 31 (03) :347-359