Imperial College London
Alternate

Professor Dame Amanda Fisher

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

amanda.fisher

 
 
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Assistant

 

Ms Alessandra Lisini +44 (0)20 3313 8236

 
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Location

 

CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ing-Simmons:2015:10.1101/gr.184986.114,
author = {Ing-Simmons, E and Seitan, VC and Faure, AJ and Flicek, P and Carroll, T and Dekker, J and Fisher, AG and Lenhard, B and Merkenschlager, M},
doi = {10.1101/gr.184986.114},
journal = {Genome Research},
pages = {504--513},
title = {Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin},
url = {http://dx.doi.org/10.1101/gr.184986.114},
volume = {25},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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, ∼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.”
AU  - Ing-Simmons,E
AU  - Seitan,VC
AU  - Faure,AJ
AU  - Flicek,P
AU  - Carroll,T
AU  - Dekker,J
AU  - Fisher,AG
AU  - Lenhard,B
AU  - Merkenschlager,M
DO  - 10.1101/gr.184986.114
EP  - 513
PY  - 2015///
SN  - 1054-9803
SP  - 504
TI  - Spatial enhancer clustering and regulation of enhancer-proximal genes by cohesin
T2  - Genome Research
UR  - http://dx.doi.org/10.1101/gr.184986.114
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000352139200005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://genome.cshlp.org/content/25/4/504
UR  - http://hdl.handle.net/10044/1/19519
VL  - 25
ER  -
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