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 Tambuwala, Stuart Brown, Anita Wdowicz, Danielle Corbett, Keith J Murphy, Catherine Godson, Eoin P. Cummins, Cormac T. Taylor, Alex Cheong

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 .
LanguageEnglish
Pages1-22
JournalScientific Reports
Volume6
Issue number31355
Early online date17 Aug 2016
DOIs
Publication statusE-pub ahead of print - 17 Aug 2016

Fingerprint

Transcriptional Silencer Elements
Transcription Factors
Genes
Gene Expression
Hypoxia
HEK293 Cells
Chromatin
RNA
Kidney

Keywords

  • Hypoxia
  • Repressor
  • REST
  • transcription.

Cite this

Cavadas, M. A. S., Mesnieres, M., Crifo, B., Manresa, M. C., Selfridge, A. C., Keogh, C. E., ... Cheong, A. (2016). REST is a hypoxia-responsive transcriptional repressor. Scientific Reports, 6(31355), 1-22. https://doi.org/10.1038/srep31355
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. ; Cheong, Alex. / REST is a hypoxia-responsive transcriptional repressor. In: Scientific Reports. 2016 ; Vol. 6, No. 31355. pp. 1-22.
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Cavadas, MAS, Mesnieres, M, Crifo, B, Manresa, MC, Selfridge, AC, Keogh, CE, Fabian, Z, Scholz, CC, Nolan, KA, Rocha, LMA, Tambuwala, M, Brown, S, Wdowicz, A, Corbett, D, Murphy, KJ, Godson, C, Cummins, EP, Taylor, CT & Cheong, A 2016, 'REST is a hypoxia-responsive transcriptional repressor', Scientific Reports, vol. 6, no. 31355, pp. 1-22. https://doi.org/10.1038/srep31355

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.; Cheong, Alex.

In: Scientific Reports, Vol. 6, No. 31355, 17.08.2016, p. 1-22.

Research output: Contribution to journalArticle

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T1 - REST is a hypoxia-responsive transcriptional repressor

AU - Cavadas, Miguel A.S.

AU - Mesnieres, Marion

AU - Crifo, Bianca

AU - Manresa, Mario C.

AU - Selfridge, Andrew C.

AU - Keogh, Ciara E.

AU - Fabian, Zsolt

AU - Scholz, Carsten C.

AU - Nolan, Karen A.

AU - Rocha, Liliane M.A.

AU - Tambuwala, Murtaza

AU - Brown, Stuart

AU - Wdowicz, Anita

AU - Corbett, Danielle

AU - Murphy, Keith J

AU - Godson, Catherine

AU - Cummins, Eoin P.

AU - Taylor, Cormac T.

AU - Cheong, Alex

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KW - REST

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M3 - Article

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JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 31355

ER -

Cavadas MAS, Mesnieres M, Crifo B, Manresa MC, Selfridge AC, Keogh CE et al. REST is a hypoxia-responsive transcriptional repressor. Scientific Reports. 2016 Aug 17;6(31355):1-22. https://doi.org/10.1038/srep31355