2024-03-29T15:05:14Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1885352023-01-31T13:04:53Zcom_10261_22com_10261_1col_10261_275
The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia
Tiana, Maria
Acosta-Iborra, Bárbara
Puente-Santamaría, Laura
Hernansanz-Agustín, Pablo
Worsley-Hunt, Rebecca
Masson, Norma
García-Río, Francisco
Peso, Luis del
Ministerio de Ciencia, Innovación y Universidades (España)
Ministerio de Ciencia e Innovación (España)
Ministerio de Economía y Competitividad (España)
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
National Institutes of Health (US)
Michael Smith Foundation for Health Research
Fundación Caja Madrid
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.
2019-08-20T07:20:56Z
2019-08-20T07:20:56Z
2018
artículo
Nucleic Acids Research 46(1): 120-133 (2018)
0305-1048
http://hdl.handle.net/10261/188535
10.1093/nar/gkx951
1362-4962
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100000245
http://dx.doi.org/10.13039/100000002
http://dx.doi.org/10.13039/501100003403
http://dx.doi.org/10.13039/501100000024
http://dx.doi.org/10.13039/501100000038
29059365
eng
Publisher's version
https://doi.org/10.1093/nar/gkx951
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-53819-R
http://creativecommons.org/licenses/by-nc/4.0/
openAccess
Oxford University Press