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Mediator and cohesin connect gene expression and chromatin architecture

Michael H. Kagey, Jamie J. Newman, Steve Bilodeau, Ye Zhan, David A. Orlando, Nynke L. van Berkum, Christopher C. Ebmeier, Jesse Goossens, Peter B. Rahl, Stuart S. Levine, Dylan J. Taatjes (), Job Dekker () and Richard A. Young ()
Additional contact information
Michael H. Kagey: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Jamie J. Newman: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Steve Bilodeau: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Ye Zhan: University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
David A. Orlando: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Nynke L. van Berkum: University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
Christopher C. Ebmeier: University of Colorado
Jesse Goossens: University of Colorado
Peter B. Rahl: Whitehead Institute for Biomedical Research, 9 Cambridge Center
Stuart S. Levine: Massachusetts Institute of Technology
Dylan J. Taatjes: University of Colorado
Job Dekker: University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
Richard A. Young: Whitehead Institute for Biomedical Research, 9 Cambridge Center

Nature, 2010, vol. 467, issue 7314, 430-435

Abstract: Abstract 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.

Date: 2010
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DOI: 10.1038/nature09380

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