UMMS Affiliation
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Publication Date
4-2015
Document Type
Article
Disciplines
Bioinformatics | Computational Biology | Genomics | Structural Biology | Systems Biology
Abstract
In addition to mediating sister chromatid cohesion during the cell cycle, the cohesin complex associates with CTCF and with active gene regulatory elements to form long-range interactions between its binding sites. Genome-wide chromosome conformation capture had shown that cohesin's main role in interphase genome organization is in mediating interactions within architectural chromosome compartments, rather than specifying compartments per se. However, it remains unclear how cohesin-mediated interactions contribute to the regulation of gene expression. We have found that the binding of CTCF and cohesin is highly enriched at enhancers and in particular at enhancer arrays or "super-enhancers" in mouse thymocytes. Using local and global chromosome conformation capture, we demonstrate that enhancer elements associate not just in linear sequence, but also in 3D, and that spatial enhancer clustering is facilitated by cohesin. The conditional deletion of cohesin from noncycling thymocytes preserved enhancer position, H3K27ac, H4K4me1, and enhancer transcription, but weakened interactions between enhancers. Interestingly, approximately 50% of deregulated genes reside in the vicinity of enhancer elements, suggesting that cohesin regulates gene expression through spatial clustering of enhancer elements. We propose a model for cohesin-dependent gene regulation in which spatial clustering of enhancer elements acts as a unified mechanism for both enhancer-promoter "connections" and "insulation."
DOI of Published Version
10.1101/gr.184986.114
Source
Genome Res. 2015 Apr;25(4):504-13. doi: 10.1101/gr.184986.114. Epub 2015 Feb 12. Link to article on publisher's site
Journal/Book/Conference Title
Genome research
Related Resources
PubMed ID
25677180
Repository Citation
Ing-Simmons, Elizabeth; Seitan, Vlad C.; Faure, Andre J.; Flicek, Paul; Carroll, Thomas; Dekker, Job; Fisher, Amanda G.; Lenhard, Boris; and Merkenschlager, Matthias, "Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin" (2015). Program in Systems Biology Publications and Presentations. 60.
https://escholarship.umassmed.edu/sysbio_pubs/60
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Included in
Bioinformatics Commons, Computational Biology Commons, Genomics Commons, Structural Biology Commons, Systems Biology Commons
Comments
© 2015 Ing-Simmons 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 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.