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Título: | The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia |
Autor: | Tiana, Maria CSIC ORCID; Acosta-Iborra, Bárbara CSIC ORCID; Puente-Santamaría, Laura; Hernansanz-Agustín, Pablo; Worsley-Hunt, Rebecca; Masson, Norma; García-Río, Francisco; Peso, Luis del CSIC ORCID | Fecha de publicación: | 2018 | Editor: | Oxford University Press | Citación: | Nucleic Acids Research 46(1): 120-133 (2018) | Resumen: | Cells 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. | Versión del editor: | https://doi.org/10.1093/nar/gkx951 | URI: | http://hdl.handle.net/10261/188535 | DOI: | 10.1093/nar/gkx951 | ISSN: | 0305-1048 | E-ISSN: | 1362-4962 |
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