Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in Drosophila
Localized H3K36 methylation states define histone H4K16 acetylation during transcriptional elongation in Drosophila
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DOI：
10.1038/sj.emboj.7601926
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发表时间：
2007-12-12
期刊：
影响因子：
11.4
通讯作者：
Schuebeler, Dirk
中科院分区：
文献类型：
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作者：
Bell, Oliver;Wirbelauer, Christiane;Schuebeler, Dirk
组蛋白的翻译后修饰参与转录起始和延伸。组蛋白 H3 (H3K36me) 赖氨酸 36 的甲基化位于酿酒酵母转录区域的启动子远端，被认为可以通过组蛋白脱乙酰酶活性的募集来防止虚假起始。在这里，我们报告了果蝇中涉及两种组蛋白甲基转移酶（HMTase）的 H3K36me 分布、调节和读出的惊人复杂性。 H3K36 的二甲基化峰值位于启动子附近，需要 dMes-4，而三甲基化则在基因 3' 端积累并依赖 dHypb。 H3K36me3 的减少对果蝇幼虫是致命的，并导致乙酰化水平升高，特别是组蛋白 H4 (H4K16ac) 的赖氨酸 16 处。相反，二甲基化和三甲基化的减少会降低赖氨酸 16 乙酰化。因此，H3K36 的二甲基化和三甲基化对 H4K16 乙酰化具有相反的影响，我们认为这能够在转录物延伸过程中实现染色质压缩的动态变化。
Post-translational modifications of histones are involved in transcript initiation and elongation. Methylation of lysine 36 of histone H3 ( H3K36me) resides promoter distal at transcribed regions in Saccharomyces cerevisiae and is thought to prevent spurious initiation through recruitment of histone-deacetylase activity. Here, we report surprising complexity in distribution, regulation and readout of H3K36me in Drosophila involving two histone methyltransferases (HMTases). Dimethylation of H3K36 peaks adjacent to promoters and requires dMes-4, whereas trimethylation accumulates toward the 3' end of genes and relies on dHypb. Reduction of H3K36me3 is lethal in Drosophila larvae and leads to elevated levels of acetylation, specifically at lysine 16 of histone H4 ( H4K16ac). In contrast, reduction of both di- and trimethylation decreases lysine 16 acetylation. Thus di- and trimethylation of H3K36 have opposite effects on H4K16 acetylation, which we propose enable dynamic changes in chromatin compaction during transcript elongation.