Mediator and cohesin connect gene expression and chromatin architecture.
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.
Kagey
Michael H
MH
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Newman
Jamie J
JJ
Bilodeau
Steve
S
Zhan
Ye
Y
Orlando
David A
DA
van Berkum
Nynke L
NL
Ebmeier
Christopher C
CC
Goossens
Jesse
J
Rahl
Peter B
PB
Levine
Stuart S
SS
Taatjes
Dylan J
DJ
Dekker
Job
J
Young
Richard A
RA
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000235:genetics*; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009690:Nucleic Acid Conformation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004247:DNA; D056892:Mediator Complex; D000097722:Cohesins