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Sci Rep. 2016 Aug 17;6:31355. doi: 10.1038/srep31355.

REST is a hypoxia-responsive transcriptional repressor.

Author information

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.

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.

PMID:
27531581
PMCID:
PMC4987654
DOI:
10.1038/srep31355
[Indexed for MEDLINE]
Free PMC Article

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