Distant cis-regulatory elements in human skeletal muscle differentiation

Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions....

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Main Authors: McCord, Rachel P., Zhou, Vicky W., Yuh, Tiffany, Bulyk, Martha L.
Other Authors: Harvard University--MIT Division of Health Sciences and Technology
Format: Article
Language:en_US
Published: Elsevier 2014
Online Access:http://hdl.handle.net/1721.1/92312
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author McCord, Rachel P.
Zhou, Vicky W.
Yuh, Tiffany
Bulyk, Martha L.
author2 Harvard University--MIT Division of Health Sciences and Technology
author_facet Harvard University--MIT Division of Health Sciences and Technology
McCord, Rachel P.
Zhou, Vicky W.
Yuh, Tiffany
Bulyk, Martha L.
author_sort McCord, Rachel P.
collection MIT
description Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions. We identify putative cis-regulatory modules (CRMs) in human skeletal muscle differentiation by combining myogenic TF binding data before and after differentiation with histone modification data in myoblasts. CRMs that are distant (> 20 kb) from muscle gene promoters are common and are more likely than proximal promoter regions to show differentiation-specific changes in myogenic TF binding. We find that two of these distant CRMs, known to activate transcription in differentiating myoblasts, interact physically with gene promoters (PDLIM3 and ACTA1) during differentiation. Our results highlight the importance of considering distal CRMs in investigations of mammalian gene regulation and support the hypothesis that distant CRM-promoter looping contacts are a general mechanism of gene regulation.
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spelling mit-1721.1/923122022-09-27T18:44:39Z Distant cis-regulatory elements in human skeletal muscle differentiation McCord, Rachel P. Zhou, Vicky W. Yuh, Tiffany Bulyk, Martha L. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Bulyk, Martha L. Yuh, Tiffany Identifying gene regulatory elements and their target genes in human cells remains a significant challenge. Despite increasing evidence of physical interactions between distant regulatory elements and gene promoters in mammalian cells, many studies consider only promoter-proximal regulatory regions. We identify putative cis-regulatory modules (CRMs) in human skeletal muscle differentiation by combining myogenic TF binding data before and after differentiation with histone modification data in myoblasts. CRMs that are distant (> 20 kb) from muscle gene promoters are common and are more likely than proximal promoter regions to show differentiation-specific changes in myogenic TF binding. We find that two of these distant CRMs, known to activate transcription in differentiating myoblasts, interact physically with gene promoters (PDLIM3 and ACTA1) during differentiation. Our results highlight the importance of considering distal CRMs in investigations of mammalian gene regulation and support the hypothesis that distant CRM-promoter looping contacts are a general mechanism of gene regulation. National Human Genome Research Institute (U.S.) (Grant R21 HG005149) 2014-12-16T13:53:18Z 2014-12-16T13:53:18Z 2011-08 2011-08 Article http://purl.org/eprint/type/JournalArticle 08887543 1089-8646 http://hdl.handle.net/1721.1/92312 McCord, Rachel Patton, Vicky W. Zhou, Tiffany Yuh, and Martha L. Bulyk. “Distant Cis-Regulatory Elements in Human Skeletal Muscle Differentiation.” Genomics 98, no. 6 (December 2011): 401–411. © 2011 Elsevier Inc. en_US http://dx.doi.org/10.1016/j.ygeno.2011.08.003 Genomics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle McCord, Rachel P.
Zhou, Vicky W.
Yuh, Tiffany
Bulyk, Martha L.
Distant cis-regulatory elements in human skeletal muscle differentiation
title Distant cis-regulatory elements in human skeletal muscle differentiation
title_full Distant cis-regulatory elements in human skeletal muscle differentiation
title_fullStr Distant cis-regulatory elements in human skeletal muscle differentiation
title_full_unstemmed Distant cis-regulatory elements in human skeletal muscle differentiation
title_short Distant cis-regulatory elements in human skeletal muscle differentiation
title_sort distant cis regulatory elements in human skeletal muscle differentiation
url http://hdl.handle.net/1721.1/92312
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