Transcription-coupled methylation of histone H3 at lysine 36 regulates dosage compensation by enhancing recruitment of the MSL complex in Drosophila melanogaster
Transcription-coupled methylation of histone H3 at lysine 36 regulates dosage compensation by enhancing recruitment of the MSL complex in Drosophila melanogaster
复制标题
DOI：
10.1128/mcb.00006-08
复制
发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Schuebeler, Dirk
中科院分区：
文献类型：
--
作者：
Bell, Oliver;Conrad, Thomas;Schuebeler, Dirk
在黑腹果蝇中，剂量补偿依赖于雄性特异性致死（MSL）复合物对雄性X染色体沿着数百个位点的靶向作用。组蛋白H3赖氨酸36的转录偶联甲基化向活性基因的3'端富集，类似于MSL蛋白。在这里，我们研究了组蛋白H3甲基化和MSL复合物靶向使用RNA干扰和染色质免疫沉淀之间的联系。我们发现，三甲基化组蛋白H3在赖氨酸36（H3K36me3）依赖于组蛋白甲基转移酶Hypb和本地化启动子远端剂量补偿基因，类似于常染色体上的活性基因。然而，H3K36me3具有X特异性功能，因为还原特异性降低男性X染色体上组蛋白H4赖氨酸16的乙酰化。这种低乙酰化是由受损的MSL结合引起的，并导致表达未能增加两倍。因此，H3K36me3标记了所有活性基因的主体，但以染色体特异性方式用于增强剂量补偿位点处的组蛋白乙酰化。
In Drosophila melanogaster, dosage compensation relies on the targeting of the male-specific lethal (MSL) complex to hundreds of sites along the male X chromosome. Transcription-coupled methylation of histone H3 lysine 36 is enriched toward the 3' end of active genes, similar to the MSL proteins. Here, we have studied the link between histone H3 methylation and MSL complex targeting using RNA interference and chromatin immunoprecipitation. We show that trimethylation of histone H3 at lysine 36 (H3K36me3) relies on the histone methyl trans ferase Hypb and is localized promoter distal at dosage-compensated genes, similar to active genes on autosomes. However, H3K36me3 has an X-specific function, as reduction specifically decreases acetylation of histone H4 lysine 16 on the male X chromosome. This hypoacetylation is caused by compromised MSL binding and results in a failure to increase expression twofold. Thus, H3K36me3 marks the body of all active genes yet is utilized in a chromosome-specific manner to enhance histone acetylation at sites of dosage compensation.