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首页> 外文期刊>Epigenetics & Chromatin >Roles for common MLL/COMPASS subunits and the 19S proteasome in regulating CIITA pIV and MHC class II gene expression and promoter methylation
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Roles for common MLL/COMPASS subunits and the 19S proteasome in regulating CIITA pIV and MHC class II gene expression and promoter methylation

机译：常见的MLL / COMPASS亚基和19S蛋白酶体在调节CIITA pIV和MHC II类基因表达以及启动子甲基化中的作用

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Background Studies indicate that the 19S proteasome contributes to chromatin reorganization, independent of the role the proteasome plays in protein degradation. We have previously shown that components of the 19S proteasome are crucial for regulating inducible histone activation events in mammalian cells. The 19S ATPase Sug1 binds to histone-remodeling enzymes, and in the absence of Sug1, a subset of activating epigenetic modifications including histone H3 acetylation, H3 lysine 4 trimethylation and H3 arginine 17 dimethylation are inhibited at cytokine-inducible major histocompatibilty complex (MHC)-II and class II transactivator (CIITA) promoters, implicating Sug1 in events required to initiate mammalian transcription. Results Our previous studies indicate that H3 lysine 4 trimethylation at cytokine-inducible MHC-II and CIITA promoters is dependent on proteolytic-independent functions of 19S ATPases. In this report, we show that multiple common subunits of the mixed lineage leukemia (MLL)/complex of proteins associated with Set I (COMPASS) complexes bind to the inducible MHC-II and CIITA promoters; that overexpressing a single common MLL/COMPASS subunit significantly enhances promoter activity and MHC-II HLA-DRA expression; and that these common subunits are important for H3 lysine 4 trimethylation at MHC-II and CIITA promoters. In addition, we show that H3 lysine 27 trimethylation, which is inversely correlated with H3 lysine 4 trimethylation, is significantly elevated in the presence of diminished 19S ATPase Sug1. Conclusion Taken together, these experiments suggest that the 19S proteasome plays a crucial role in the initial reorganization of events enabling the relaxation of the repressive chromatin structure surrounding inducible promoters.
机译：背景研究表明19S蛋白酶体有助于染色质重组，而与蛋白酶体在蛋白质降解中的作用无关。先前我们已经表明19S蛋白酶体的成分对于调节哺乳动物细胞中可诱导的组蛋白活化事件至关重要。 19S ATPase Sug1与组蛋白重塑酶结合，在不存在Sug1的情况下，在细胞因子诱导的主要组织相容性复合物（MHC）上抑制了包括组蛋白H3乙酰化，H3赖氨酸4三甲基化和H3精氨酸17甲基化在内的活化表观修饰。 -II和II类反式激活因子（CIITA）启动子，在启动哺乳动物转录所需的事件中涉及Sug1。结果我们以前的研究表明，在细胞因子诱导的MHC-II和CIITA启动子上的H3赖氨酸4三甲基化依赖于19S ATPase的蛋白水解独立功能。在本报告中，我们显示了混合谱系白血病（MLL）/与Set I（COMPASS）复合物相关的蛋白质复合物的多个常见亚基与诱导型MHC-II和CIITA启动子结合;过表达单个共同的MLL / COMPASS亚基可显着增强启动子活性和MHC-II HLA-DRA表达;并且这些共同的亚基对于MHC-II和CIITA启动子上的H3赖氨酸4三甲基化很重要。此外，我们显示，在19S ATPase Sug1减少的情况下，H3赖氨酸27三甲基化与H3赖氨酸4三甲基化呈负相关，并且显着提高。结论综上所述，这些实验表明19S蛋白酶体在事件的初始重组中起着至关重要的作用，使事件能够使诱导型启动子周围的染色质结构松弛。

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