REST is a hypoxia-responsive transcriptional repressor


Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxiadependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences
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Uncontrolled Keywords: hypoxia,repressor,REST ,transcription,General
Publication ISSN: 2045-2322
Last Modified: 03 Jun 2024 07:22
Date Deposited: 20 Jul 2016 10:25
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2016-08-17
Published Online Date: 2016-08-17
Accepted Date: 2016-07-18
Submitted Date: 2016-04-20
Authors: Cavadas, Miguel A.S.
Mesnieres, Marion
Crifo, Bianca
Manresa, Mario C.
Selfridge, Andrew C.
Keogh, Ciara E.
Fabian, Zsolt
Scholz, Carsten C.
Nolan, Karen A.
Rocha, Liliane M.A.
Tambuwala, Murtaza M.
Brown, Stuart
Wdowicz, Anita
Corbett, Danielle
Murphy, Keith J.
Godson, Catherine
Cummins, Eoin P.
Taylor, Cormac T.
Cheong, Alex (ORCID Profile 0000-0003-2482-9078)



Version: Published Version

License: Creative Commons Attribution

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