Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast.
Set3 contributes to heterochromatin integrity by promoting transcription of subunits of Clr4-Rik1-Cul4 histone methyltransferase complex in fission yeast.
复制标题
Set3 通过促进裂殖酵母中 Clr4-Rik1-Cul4 组蛋白甲基转移酶复合物亚基的转录来促进异染色质完整性
DOI：
10.1038/srep31752
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发表时间：
2016-08-19
影响因子：
4.6
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Yu Y;Zhou H;Deng X;Wang W;Lu H
裂解酵母中异染色质的形成依赖于RNAi机制和组蛋白修饰酶。组蛋白修饰的关键复合体之一是CLR4-Rik1-CUL4甲基转移酶复合体(CLRC)，它介导组蛋白H3K9甲基化，这是异染色质的标志。CLRC由CLR4组蛋白甲基转移酶、Rik1、Raf1、Raf2和Pcu4组成。然而，对CLRC亚单位的转录调控还不是很清楚。在本研究中，我们发现Set3/Hos2组蛋白脱乙酰酶复合体(Set3C)的核心亚单位Set3对着丝粒、端粒和沉默交配型基因座上异染色质的完整性和沉默起着重要作用。Set3的这种新的作用依赖于它的PhD手指，但与Set3C的脱乙酰酶活性或结构完整性无关。Set3不位于着丝粒区域。相反，Set3的目标是clr4+andrik1+的启动子，可能是通过它的博士手指。Set3促进clr4+和andrik1+的转录。在这3个Δ突变体中，CLR4和Rik1的蛋白水平一直在下降。这3个Δ突变体的异染色质沉默缺陷可以通过Clr4+或rik1+的过表达来挽救。我们的研究表明，基本异染色质因子的转录激活是异染色质完整性严格调控的基础。
Heterochromatin formation in fission yeast depends on RNAi machinery and histone-modifying enzymes. One of the key histone-modifying complexes is Clr4-Rik1-Cul4 methyltransferase complex (CLRC), which mediates histone H3K9 methylation, a hallmark for heterochromatin. CLRC is composed of the Clr4 histone methyltransferase, Rik1, Raf1, Raf2 and Pcu4. However, transcriptional regulation of the CLRC subunits is not well understood. In this study, we identified Set3, a core subunit of the Set3/Hos2 histone deacetylase complex (Set3C), as a contributor to the integrity and silencing of heterochromatin at centromeres, telomeres and silent mating-type locus. This novel role of Set3 relies on its PHD finger, but is independent of deacetylase activity or structural integrity of Set3C. Set3 is not located to the centromeric region. Instead, Set3 is targeted to the promoters ofclr4+andrik1+, probably through its PHD finger. Set3 promotes transcription ofclr4+andrik1+. Consistently, the protein levels of Clr4 and Rik1 were reduced in theset3Δ mutant. The heterochromatin silencing defect in theset3Δ mutant could be rescued by overexpressing ofclr4+orrik1+. Our study suggests transcriptional activation of essential heterochromatin factors underlies the tight regulation of heterochromatin integrity.