Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation
Ubiquitylation of the COMPASS component Swd2 links H2B ubiquitylation to H3K4 trimethylation
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DOI：
10.1038/ncb1796
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发表时间：
2008-11-01
影响因子：
21.3
通讯作者：
Dargemont, Catherine
中科院分区：
文献类型：
--
作者：
Vitaliano-Prunier, Adeline;Menant, Alexandra;Dargemont, Catherine
组蛋白H2B的单泛素化与转录激活相关，并且是SET1/COMPASS甲基转移酶复合物在组蛋白H3尾部（H3K4）的第4赖氨酸二甲基化和三甲基化所必需的，这种甲基化通过一个特征不明确的反尾途径进行（1,2）。本研究表明，组蛋白H2B的单泛素化促进了酿酒酵母SET1/COMPASS的重要组成部分Swd2的第68和69位泛素化。我们发现负责H2B泛素化的Rad6/Bre1泛素化酶也直接参与Swd2修饰。阻止Swd2或H2B泛素化并不影响Set1的稳定性、Swd2与Set1的相互作用或Swd2与染色质相互作用的能力。然而，我们发现Swd2的Lys 68和Lys 69突变显著降低了转录基因5'端H3K4的三甲基化，并在较小程度上降低了二甲基化，而不影响单甲基化。这种效应是由于Swd2泛素化能够控制Spp1的募集，Spp1是COMPASS亚基三甲基化所必需的。我们的研究结果进一步表明Swd2是COMPASS的主要h3结合成分。因此，Swd2是介导染色质上H2B泛素化和H3K4三甲基化之间串扰的关键因子。
Mono-ubiquitylation of histone H2B correlates with transcriptional activation and is required for di- and trimethylation at Lys 4 on the histone H3 tail (H3K4) by the SET1/COMPASS methyltransferase complex through a poorly characterized trans-tail pathway(1,2). Here we show that mono-ubiquitylation of histone H2B promotes ubiquitylation at Lys 68 and Lys 69 of Swd2, the essential component of SET1/COMPASS in Saccharomyces cerevisiae. We found that Rad6/Bre1 ubiquitylation enzymes responsible for H2B ubiquitylation also participate directly in Swd2 modification. Preventing Swd2 or H2B ubiquitylation did not affect Set1 stability, interaction of Swd2 with Set1 or the ability of Swd2 to interact with chromatin. However, we found that mutation of Lys 68 and Lys 69 of Swd2 markedly reduced trimethylation, and to a lesser extent dimethylation, of H3K4 at the 5'- end of transcribing genes without affecting monomethylation. This effect results from the ability of Swd2 ubiquitylation to control recruitment of Spp1, a COMPASS subunit necessary for trimethylation. Our results further indicate that Swd2 is a major H3-binding component of COMPASS. Swd2 thus represents a key factor that mediates crosstalk between H2B ubiquitylation and H3K4 trimethylation on chromatin.