REST is a hypoxia-responsive transcriptional repressor

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. and Cheong, Alex (2016). REST is a hypoxia-responsive transcriptional repressor. Scientific Reports, 6 ,

Abstract

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.

Publication DOI: https://doi.org/10.1038/srep31355
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Additional Information: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The imageor other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: hypoxia,repressor,REST ,transcription,General
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-08-17
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 ( 0000-0003-2482-9078)

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