Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex
Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex
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DOI：
10.1016/j.cell.2005.10.025
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发表时间：
2005-11-08
期刊：
影响因子：
64.5
通讯作者：
Krogan, NJ
中科院分区：
文献类型：
--
作者：
Keogh, MC;Kurdistani, SK;Krogan, NJ
酵母组蛋白去乙酰化酶Rpd3可被招募到启动子以抑制转录起始。生化、遗传和基因表达分析表明，Rpd3存在于两种不同的复合物中。较小的复合物Rpd3C(S)与Rpd3C(L)共享Sin3和Ume1，但含有独特的亚基Rco1和Eaf3。Rpd3C(S)突变体表现出与Set2极为相似的表型，Set2是一种与延伸的RNA聚合酶II相关的组蛋白甲基转移酶。染色质免疫沉淀和生化实验表明，Eaf3的染色质结构域将Rpd3C(S)招募到由Set2在组蛋白H3赖氨酸36上甲基化的核小体，导致转录区域的去乙酰化。该途径显然起到负调控转录的作用，因为缺失Set2或Rpd3C(S)的基因可绕过对正性延伸因子Bur1/Bur2的需求。
The yeast histone deacetylase Rpd3 can be recruited to promoters to repress transcription initiation. Biochemical, genetic, and gene-expression analyses show that Rpd3 exists in two distinct complexes. The smaller complex, Rpd3C(S), shares Sin3 and Ume1 with Rpd3C(L) but contains the unique subunits Rco1 and Eaf3. Rpd3C(S) mutants exhibit phenotypes remarkably similar to those of Set2, a histone methyltransferase associated with elongating RNA polymerase II. Chromatin immunoprecipitation and biochemical experiments indicate that the chromodomain of Eaf3 recruits Rpd3C(S) to nucleosomes methylated by Set2 on histone H3 lysine 36, leading to deacetylation of transcribed regions. This pathway apparently acts to negatively regulate transcription because deleting the genes for Set2 or Rpd3C(S) bypasses the requirement for the positive elongation factor Bur1/ Bur2.