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

doi:10.1038/srep31355

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

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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 .

Original language	English
Article number	31355 (2016)
Number of pages	22
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep31355
Publication status	Published (in print/issue) - 17 Aug 2016

Keywords

Hypoxia
Repressor
REST
transcription.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Accepted author manuscript PDFAuthor Accepted Manuscript, 10 MBLicence: CC BY

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Cavadas, M. A. S., Mesnieres, M., Crifo, B., Manresa, M. C., Selfridge, A. C., Keogh, C. E., Fabian, Z., Scholz, C. C., Nolan, K. A., Rocha, L. M. A., Tambuwala, M., Brown, S., Wdowicz, A., Corbett, D., Murphy, K. J., Godson, C., Cummins, E. P., Taylor, C. T., & Cheong, A. (2016). REST is a hypoxia-responsive transcriptional repressor. Scientific Reports, 6, Article 31355 (2016) . https://doi.org/10.1038/srep31355

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title = "REST is a hypoxia-responsive transcriptional repressor",

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 .",

keywords = "Hypoxia, Repressor, REST, transcription.",

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

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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, 31355 (2016) . https://doi.org/10.1038/srep31355

TY - JOUR

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

PY - 2016/8/17

Y1 - 2016/8/17

N2 - 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 .

AB - 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 .

KW - Hypoxia

KW - Repressor

KW - REST

KW - transcription.

UR - http://www.nature.com/articles/srep31355

UR - https://pure.ulster.ac.uk/en/publications/rest-is-a-hypoxia-responsive-transcriptional-repressor-3

U2 - 10.1038/srep31355

DO - 10.1038/srep31355

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 31355 (2016)

ER -

REST is a hypoxia-responsive transcriptional repressor

Abstract

Keywords

UN SDGs

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