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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, 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 (31355). pp. 1-22. [Journal article]

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URL: http://www.nature.com/articles/srep31355

DOI: 10.1038/srep31355

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 immuno precipitation 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 .

Item Type:Journal article
Keywords:Hypoxia, Repressor, REST, transcription.
Faculties and Schools:Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:35621
Deposited By: Dr Murtaza Tambuwala
Deposited On:08 Aug 2016 08:40
Last Modified:17 Oct 2017 16:25

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