Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
SCREDS Clinical Lecturer in Plastic and Reconstructive Surgery, Centre for Cell Engineering, University of Glasgow, Glasgow G12 8QQ, U.K.
Biochem J. 2018 Jun 29;475(12):2073-2090. doi: 10.1042/BCJ20170945.
The SIN3A-HDAC (histone deacetylase) complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF (SIN3A and HDAC-associated factor)/FAM60A (family of homology 60A), links the SIN3A-HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically represses HIF-2α mRNA and protein expression, via its interaction with the transcription factor SP1 (specificity protein 1) and recruitment of HDAC1 to the HIF-2α promoter. SINHCAF control over HIF-2α results in functional cellular changes in angiogenesis and viability. Our analysis reveals an unexpected link between SINHCAF and the regulation of the hypoxia response.
SIN3A-HDAC（组蛋白去乙酰化酶）复合物是一种主要的转录抑制因子，对于发育是必需的，但在疾病中经常失调。在这里，我们报告说，这个复合物的最近确定的新成分，SINHCAF（SIN3A 和 HDAC 相关因子）/FAM60A（同源性 60A 家族），将 SIN3A-HDAC 共抑制复合物的功能与低氧反应联系起来。我们表明，SINHCAF 通过与转录因子 SP1（特异性蛋白 1）相互作用并将 HDAC1 募集到 HIF-2α 启动子，特异性地抑制 HIF-2α mRNA 和蛋白表达。SINHCAF 对 HIF-2α 的控制导致血管生成和活力的功能细胞变化。我们的分析揭示了 SINHCAF 与缺氧反应调节之间的意外联系。
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