REST is a hypoxia-responsive transcriptional repressor

Miguel A.S. Cavadas, Marion Mesnieres, Bianca Crifo, Mario C. Manresa, Andrew C. Selfridge, Ciara E. Keogh, Zsolt Fabian, Carsten C. Scholz, Karen A. Nolan, Liliane M.A. Rocha, Murtaza M. Tambuwala, Stuart Brown, Anita Wdowicz, Danielle Corbett, Keith J. Murphy, Catherine Godson, Eoin P. Cummins, Cormac T. Taylor, Alex Cheong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number31355
Number of pages13
JournalScientific Reports
Volume6
Early online date17 Aug 2016
DOIs
Publication statusPublished - 17 Aug 2016

Bibliographical note

© 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/

Keywords

  • hypoxia
  • repressor
  • REST
  • transcription

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