UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Date

12-1-2013

Document Type

Article

Disciplines

Genetics and Genomics | Systems Biology

Abstract

Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements, but its precise function and mechanistic basis remain unknown. Cohesin controls chromosome topology to enable DNA repair and chromosome segregation in cycling cells. In addition, cohesin associates with active enhancers and promoters and with CTCF to form long-range interactions important for gene regulation. Although these findings suggest an important role for cohesin in genome organization, this role has not been assessed on a global scale. Unexpectedly, we find that architectural compartments are maintained in non-cycling mouse thymocytes after genetic depletion of cohesin in vivo. Cohesin was however required for specific long-range interactions within compartments where cohesin-regulated genes reside. Cohesin depletion diminished interactions between cohesin-bound sites, while alternative interactions between chromatin features associated with transcriptional activation and repression became more prominent, with corresponding changes in gene expression. Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within pre-existing chromosomal compartments.

Rights and Permissions

Citation: Seitan V, Faure A, Zhan Y, McCord R, Lajoie B, Ing-Simmons E, Lenhard B, Giorgetti L, Heard E, Fisher A, Flicek P, Dekker J, Merkenschlager M. Cohesin-based chromatin interactions enable regulated gene expression within pre-existing architectural compartments. Genome Res. 2013 Dec;23(12):2066-77. doi: 10.1101/gr.161620.113. Published in advance 2013 Sep 3. Link to article on publisher's site

Comments

© 2013 Seitan et al.; Published by Cold Spring Harbor Laboratory Press.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

Related Resources

Link to Article in PubMed

Journal Title

Genome research

PubMed ID

24002784

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