Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/38805
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dc.contributor.authorTiana, Maria
dc.contributor.authorAcosta-Iborra, Barbara
dc.contributor.authorPuente-Santamaría, Laura
dc.contributor.authorHernansanz-Agustin, Pablo
dc.contributor.authorWorsley-Hunt, Rebecca
dc.contributor.authorMasson, Norma
dc.contributor.authorGarcía-Rio, Francisco
dc.contributor.authorMole, David
dc.contributor.authorRatcliffe, Peter
dc.contributor.authorWasserman, Wyeth W
dc.contributor.authorJimenez, Benilde
dc.contributor.authorDel Peso, Luis
dc.date.accessioned2019-06-28T18:55:46Z-
dc.date.available2019-06-28T18:55:46Z-
dc.date.issued2018
dc.identifier.citationNucleic Acids Res..2018 01;(46)1:120-133
dc.identifier.urihttps://hdl.handle.net/20.500.12530/38805-
dc.description.abstractCells adapt to environmental changes, including fluctuations in oxygen levels, through the induction of specific gene expression programs. To identify genes regulated by hypoxia at the transcriptional level, we pulse-labeled HUVEC cells with 4-thiouridine and sequenced nascent transcripts. Then, we searched genome-wide binding profiles from the ENCODE project for factors that correlated with changes in transcription and identified binding of several components of the Sin3A co-repressor complex, including SIN3A, SAP30 and HDAC1/2, proximal to genes repressed by hypoxia. SIN3A interference revealed that it participates in the downregulation of 75% of the hypoxia-repressed genes in endothelial cells. Unexpectedly, it also blunted the induction of 47% of the upregulated genes, suggesting a role for this corepressor in gene induction. In agreement, ChIP-seq experiments showed that SIN3A preferentially localizes to the promoter region of actively transcribed genes and that SIN3A signal was enriched in hypoxia-repressed genes, prior exposure to the stimulus. Importantly, SINA3 occupancy was not altered by hypoxia in spite of changes in H3K27ac signal. In summary, our results reveal a prominent role for SIN3A in the transcriptional response to hypoxia and suggest a model where modulation of the associated histone deacetylase activity, rather than its recruitment, determines the transcriptional output.
dc.language.isoeng
dc.rightsopenAccess-
dc.titleThe SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia.
dc.typeArtículo
dc.identifier.pubmedID29059365
dc.format.volume46
dc.format.page120-133
dc.identifier.e-issn1362-4962
dc.identifier.journalNucleic acids research
dc.identifier.doi10.1093/nar/gkx951
dc.format.number1
dc.identifier.pmcPMC5758878
dc.pubmedtypeJournal Article
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.pubmedtypeResearch Support, N.I.H., Extramural
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. La Princesa > Artículos
Fundaciones e Institutos de Investigación > IIS H. U. La Paz > Artículos

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