Multiple histone deacetylases are recruited by corepressor Sin3 and contribute to gene repression mediated by Opi1 regulator of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae

Yeast genes of phospholipid biosynthesis are negatively regulated by repressor protein Opi1 when precursor molecules inositol and choline (IC) are available. Opi1-triggered gene repression is mediated by recruitment of the Sin3 corepressor complex. In this study, we systematically investigated the regulatory contribution of subunits of Sin3 complexes and identified Pho23 as important for IC-dependent gene repression. Two non-overlapping regions within Pho23 mediate its direct interaction with Sin3. Previous work has shown that Sin3 recruits the histone deacetylase (HDAC) Rpd3 to execute gene repression. While deletion of SIN3 strongly alleviates gene repression by IC, an rpd3 null mutant shows almost normal regulation. We thus hypothesized that various HDACs may contribute to Sin3-mediated repression of IC-regulated genes. Indeed, a triple mutant lacking HDACs, Rpd3, Hda1 and Hos1, could phenocopy a sin3 single mutant. We show that these proteins are able to contact Sin3 in vitro and in vivo and mapped three distinct HDAC interaction domains, designated HID1, HID2 and HID3. HID3, which is identical to the previously described structural motif PAH4 (paired amphipathic helix), can bind all HDACs tested. Chromatin immunoprecipitation studies finally confirmed that Hda1 and Hos1 are recruited to promoters of phospholipid biosynthetic genes INO1 and CHO2.     

NRSE 与 NRSF 及其对神经元特异性基因表达的调控作用

神经限制性沉默元件 (NRSE) 是一段长度为 21~23 bp 的保守 DNA 序列,存在于许多神经元特异表达基因的转录调控区中,神经限制性沉默因子 (NRSF) 能特异性结合到 NRSE dsDNA 上,并通过其 N 端和 C 端阻遏结构域分别连接共阻遏蛋白 Sin3A/B 和 CoREST , Sin3A 招募 HDAC 对组蛋白进行去乙酰基化修饰, CoREST 则作为平台蛋白招募特异的“沉默组件”,以此维持基因沉默 . 最近的研究显示, NRSE dsRNA 能在转录水平与 NRSF 蛋白直接作用,而不是作为 siRNA 或 miRNA 在转录后水平启动神经元特异性基因的表达 .