Cohesin-based chromatin interactions enable regulated gene expression within pre-existing architectural compartments
- Vlad Seitan1,
- Andre Faure2,
- Ye Zhan3,
- Rachel McCord3,
- Bryan Lajoie3,
- Elizabeth Ing-Simmons1,
- Boris Lenhard1,
- Luca Giorgetti4,
- Edith Heard4,
- Amanda Fisher1,
- Paul Flicek2,
- Job Dekker3 and
- Matthias Merkenschlager1,5
- 1 MRC Clinical Sciences Centre, Imperial College London;
- 2 European Bioinformatics Institute;
- 3 University of Massachusetts Medical School;
- 4 Institut Curie
- ↵* Corresponding author; email: matthias.merkenschlager{at}csc.mrc.ac.uk
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.
- Received June 5, 2013.
- Accepted August 28, 2013.
- © 2013, Published by Cold Spring Harbor Laboratory Press
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