The 19S proteasome positively regulates histone methylation at cytokine inducible genes
The 19S proteasome positively regulates histone methylation at cytokine inducible genes
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DOI：
10.1016/j.bbagrm.2009.07.006
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发表时间：
2009-11-01
影响因子：
4.7
通讯作者：
Greer, Susanna F.
中科院分区：
文献类型：
--
作者：
Koues, Olivia I.;Dudley, R. Kyle;Greer, Susanna F.
研究表明，19 S蛋白酶体在转录的表观遗传调控中起作用。我们已经表明，在酵母中的19 S蛋白酶体的组成部分是至关重要的调节诱导组蛋白乙酰化的哺乳动物细胞中的事件。19 S ATP酶Sug 1与组蛋白乙酰转移酶和乙酰化组蛋白H3结合，并且在不存在Sug 1的情况下，组蛋白H3乙酰化在哺乳动物启动子处显著降低。在酵母中的研究进一步表明，Sug 1的直系同源物Rpt 6是组蛋白H2 B泛素化和H3赖氨酸4三甲基化（H3 K4 me 3）之间的联系。为了表征19 S蛋白酶体在调节额外的活化修饰中所起的作用，我们研究了诱导型哺乳动物基因组蛋白的甲基化和泛素化状态。我们发现，Sug 1是至关重要的调节组蛋白H3 K4 me 3和H3 R17 me 2在细胞因子诱导型MHC-II和CIITA启动子。在缺乏Sug 1的情况下，组蛋白H3 K4 me 3和H3 R17 me 2显著减少，但Sug 1的缺失对H3 K36 me 3或H2 BK 120 ub没有显著影响。我们观察到hCompass的一个亚基与其他激活组蛋白修饰酶相互作用，但在不存在Sug 1的情况下未能结合CIITA启动子，这强烈暗示Sug 1在招募负责启动哺乳动物转录的酶复合物中。(C)2009爱思唯尔有限公司版权所有。
Studies indicate that the 19S proteasome functions in the epigenetic regulation of transcription. We have shown that as in yeasty components of the 19S proteasome are crucial for regulating inducible histone acetylation events in mammalian cells. The 19S ATPase Sug1 binds to histone acetyltransferases and to acetylated histone H3 and, in the absence of Sug1, histone H3 acetylation is dramatically decreased at mammalian promoters. Research in yeast further indicates that the ortholog of Sug1, Rpt6, is a link between ubiquitination of histone H2B and H3 lysine 4 trimethylation (H3K4me3). To characterize the role that the 19S proteasome plays in regulating additional activating modifications, we examined the methylation and ubiquitination status of histones at inducible mammalian genes. We find that Sug1 is crucial for regulating histone H3K4me3 and H3R17me2 at the cytokine inducible MHC-II and CIITA promoters. In the absence of Sug1, histone H3K4me3 and H3R17me2 are dramatically decreased, but the loss of Sug1 has no significant effect on H3K36me3 or H2BK120ub. Our observation that a subunit of hCompass interacts with additional activating histone modifying enzymes, but fails to bind the CIITA promoter in the absence of Sug1, strongly implicates Sug1 in recruiting enzyme complexes responsible for initiating mammalian transcription. (C) 2009 Elsevier B.V. All rights reserved.