SIN3A, Generally Regarded as a Transcriptional Repressor, Is Required for Induction of Gene Transcription by the Aryl Hydrocarbon Receptor

Solaimani, Parrisa; Wang, Feng; Hankinson, Oliver

doi:10.1074/jbc.m114.611236

Cited by 16 publications

(15 citation statements)

References 45 publications

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“…Although these results might seem paradoxical, SIN3A was initially described in yeast as a protein with dual functions as activator and repressor ( 68 , 69 ) and recent works are putting forward its role as an activator of specific genes (reviewed in 36 ). Of particular relevance to our work, previous works suggest that the SIN3A HDAC complex is required for the induction of genes in response to environmental insults such as heat or osmotic stress ( 64 , 65 ) in yeast and xenobiotics in mammalian cells ( 70 ). Thus, additionally to its undisputed role as corepressor, SIN3A seems to be also playing a role on transcriptional activation.…”

Section: Discussionmentioning

confidence: 76%

The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia

Tiana

Acosta‐Iborra

Puente-Santamaría

et al. 2017

Nucleic Acids Research

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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.

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Section: Discussionmentioning

confidence: 76%

The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia

Tiana

Acosta‐Iborra

Puente-Santamaría

et al. 2017

Nucleic Acids Research

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“…has wider role on transcriptional regulation. In agreement, SIN3A was initially described in yeast as a protein with dual functions as activator and repressor [116,117] and recent studies are putting forward its role as an activator of specific genes [86], including targets of the aryl hydrocarbon receptor (ARNT), a transcription factor related to HIF, known to mediate the transcriptional response to xenobiotics [118].…”

Section: Sin3a-hdacmentioning

confidence: 88%

Hypoxia and Chromatin, a Focus on Transcriptional Repression Mechanisms

Batie

Peso

Rocha

2018

Preprint

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Hypoxia, or reduced oxygen availability, has been studied extensively for its ability to activate specific genes. Hypoxia induced gene expression is mediated by the HIF transcription factors, although not exclusively so. Despite the great knowledge on the mechanisms by which hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms, but also the potential roles of dioxygenases with functions at the nucleosome and DNA level. Finally, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia.

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“…These results suggest that, beyond its function as co-repressor, SIN3A has a wider role in transcriptional regulation. SIN3A was initially described in yeast as a protein with dual functions of being an activator and a repressor [ 121 , 122 ] and recent studies are putting forward its role as an activator of specific genes [ 92 ] including targets of the aryl hydrocarbon receptor (AHR), which is a transcription factor related to HIF known to mediate the transcriptional response to xenobiotics [ 123 ]. Moreover, the dual role of SIN3A in transcriptional repression and activation in response to hypoxia is not unique to this repressor complex.…”

Section: Transcriptional Repression Complexes In Hypoxiamentioning

confidence: 99%

Hypoxia and Chromatin: A Focus on Transcriptional Repression Mechanisms

2018

View full text Add to dashboard Cite

Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms as well as the potential roles of dioxygenases with functions at the nucleosome and DNA level. Lastly, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia.

show abstract

SIN3A, Generally Regarded as a Transcriptional Repressor, Is Required for Induction of Gene Transcription by the Aryl Hydrocarbon Receptor

Cited by 16 publications

References 45 publications

The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia

The SIN3A histone deacetylase complex is required for a complete transcriptional response to hypoxia

Hypoxia and Chromatin, a Focus on Transcriptional Repression Mechanisms

Hypoxia and Chromatin: A Focus on Transcriptional Repression Mechanisms

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