Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions.
Dimethylation of H3K4 by Set1 recruits the Set3 histone deacetylase complex to 5' transcribed regions.
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DOI：
10.1016/j.cell.2009.02.045
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发表时间：
2009-04-17
期刊：
影响因子：
64.5
通讯作者：
Buratowski S
中科院分区：
文献类型：
--
作者：
Kim T;Buratowski S
Set1和Set2进行的共转录组蛋白甲基化已被证明分别影响基因启动子和3′区域的组蛋白乙酰化。虽然组蛋白H3K4三甲基化（H3K4me3）被认为促进启动子附近的核小体乙酰化和重塑，但我们在此表明Set1介导的H3K4二甲基化（H3K4me2）导致基因5′端附近的组蛋白乙酰化水平降低。H3K4me2通过Set3的PHD结构域招募Set3复合物，使Hos2和Hst1亚基定位在5′转录区域使组蛋白去乙酰化。缺乏Set1 - Set3复合物通路的细胞对霉酚酸敏感，并且在一个Set3靶基因处聚合酶水平降低，这表明其在转录中具有积极作用。我们提出Set1在基因上建立了两个不同的染色质区域：H3K4me3导致启动子处高水平的乙酰化和低核小体密度，而在下游的H3K4me2招募Set3复合物以抑制核小体乙酰化和重塑。
Co-transcriptional histone methylations by Set1 and Set2 have been shown to affect histone acetylation at promoters and 3′ regions of genes, respectively. While histone H3K4 trimethylation (H3K4me3) is thought to promote nucleosome acetylation and remodeling near promoters, we show here that H3K4 dimethylation (H3K4me2) by Set1 leads to reduced histone acetylation levels near 5′ ends of genes. H3K4me2 recruits the Set3 complex via the Set3 PHD finger, localizing the Hos2 and Hst1 subunits to deacetylate histones in 5′ transcribed regions. Cells lacking the Set1-Set3 complex pathway are sensitive to mycophenolic acid and have reduced polymerase levels at a Set3 target gene, suggesting a positive role in transcription. We propose that Set1 establishes two distinct chromatin zones on genes: H3K4me3 leads to high levels of acetylation and low nucleosome density at promoters, while H3K4me2 just downstream recruits the Set3 complex to suppress nucleosome acetylation and remodeling.
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