2. Academic Validation
  3. REST is a hypoxia-responsive transcriptional repressor

REST is a hypoxia-responsive transcriptional repressor

  • Sci Rep. 2016 Aug 17;6:31355. doi: 10.1038/srep31355.
Miguel A S Cavadas 1 2 3,  Marion Mesnieres 2,  Bianca Crifo 2,  Mario C Manresa 2,  Andrew C Selfridge 2,  Ciara E Keogh 2,  Zsolt Fabian 2,  Carsten C Scholz 1 2 4,  Karen A Nolan 4 5,  Liliane M A Rocha 6,  Murtaza M Tambuwala 7,  Stuart Brown 8,  Anita Wdowicz 9,  Danielle Corbett 9,  Keith J Murphy 9,  Catherine Godson 5,  Eoin P Cummins 2,  Cormac T Taylor 1 2,  Alex Cheong 1 2 10
Affiliations

Affiliations

  • 1 Systems Biology Ireland, University College Dublin, Dublin 4, Ireland.
  • 2 Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.
  • 3 Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 2780-156 Oeiras, Portugal.
  • 4 Institute of Physiology and Zurich Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
  • 5 Diabetes Complications Research Centre, School of Medicine and Medical Sciences, University College Dublin, Dublin 4, Ireland.
  • 6 Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal.
  • 7 School of Pharmacy and Pharmaceutical Sciences, University of Ulster, Coleraine, Co. Londonderry, BT52 1SA, Northern Ireland, UK.
  • 8 Center for Health Informatics and Bioinformatics, New York University School of Medicine, New York, NY 10016, USA.
  • 9 Neurotherapeutics Research Group, UCD School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
  • 10 Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK.
PMID: 27531581 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 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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