Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation
Two Saccharomyces cerevisiae JmjC domain proteins demethylate histone H3 Lys36 in transcribed regions to promote elongation
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DOI：
10.1074/jbc.m703034200
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发表时间：
2007-07-20
影响因子：
4.8
通讯作者：
Buratowski, Stephen
中科院分区：
文献类型：
--
作者：
Kim, TaeSoo;Buratowski, Stephen
组蛋白甲基化是一种可逆修饰，受残基特异性组蛋白甲基转移酶和去甲基化酶的拮抗功能调节。尽管组蛋白 H3 在赖氨酸 4 和 36 处的甲基化与转录相关，但组蛋白去甲基化酶在转录调控中的作用尚不清楚。在这里，我们表明，Jhd1 或 Rph1（两种 JmjC 结构域蛋白）的过表达绕过了对正延伸因子基因 BUR1 的要求。生化分析和染色质免疫沉淀实验表明，Rph1 作为 H3 K36me3 和 K36me2 的特异性去甲基化酶，直接调节转录区域的 Lys(36) 甲基化。 Jhd1 和 Rph1 都是正常水平的 RNA 聚合酶 II 与基因交联所必需的。总而言之，这些发现表明 H3 Lys(36) 组蛋白去甲基化酶的一般功能是通过拮抗 Set2 的抑制性 Lys(36) 甲基化来促进转录延伸。
Histone methylation is a reversible modification regulated by the antagonistic functions of residue-specific histone methyl-transferases and demethylases. Although methylation of histone H3 at lysines 4 and 36 is linked to transcription, the roles of histone demethylases in transcription regulation are not understood. Here we show that overexpression of either Jhd1 or Rph1, two JmjC-domain proteins, bypasses the requirement for the positive elongation factor gene BUR1. Biochemical analysis and chromatin immunoprecipitation experiments indicate that Rph1 functions as a specific demethylase for H3 K36me3 and K36me2, directly regulating Lys(36) methylation in transcribed regions. Both Jhd1 and Rph1 are required for normal levels of RNA polymerase II cross-linking to genes. Taken together, these findings indicate that a general function of histone demethylases for H3 Lys(36) is to promote transcription elongation by antagonizing repressive Lys(36) methylation by Set2.