| Autor: |
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 |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Scientific Reports |
| ISSN: |
2045-2322 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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