REST is a hypoxia-responsive transcriptional repressor

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Title: REST is a hypoxia-responsive transcriptional repressor
Authors: Cavadas, Miguel A. S.
Mesnieres, Marion
Crifo, Bianca
Manresa, Mario C.
Selfridge, Andrew C.
Keogh, Ciara E.
Fábián, 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
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Date: 17-Aug-2016
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 hypoxia-dependent 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.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Springer Nature
Keywords: HIFHEK293RESTHypoxia-responsiveHypoxiaHypoxia-inducible factor
DOI: 10.1038/srep31355
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
SBI Research Collection
Medicine Research Collection

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