组蛋白H3赖氨酸36的共转录Set2甲基化招募了一个抑制性的Rpd3复合物。

Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex.

作者信息

Keogh Michael-Christopher, Kurdistani Siavash K, Morris Stephanie A, Ahn Seong Hoon, Podolny Vladimir, Collins Sean R, Schuldiner Maya, Chin Kayu, Punna Thanuja, Thompson Natalie J, Boone Charles, Emili Andrew, Weissman Jonathan S, Hughes Timothy R, Strahl Brian D, Grunstein Michael, Greenblatt Jack F, Buratowski Stephen, Krogan Nevan J

机构信息

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

Cell. 2005 Nov 18;123(4):593-605. doi: 10.1016/j.cell.2005.10.025.

DOI:10.1016/j.cell.2005.10.025

PMID:16286008

Abstract

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.

摘要

酵母组蛋白去乙酰化酶Rpd3可被招募至启动子以抑制转录起始。生化、遗传学及基因表达分析表明，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，但包含独特的亚基Rco1和Eaf3。Rpd3C(S)突变体表现出与Set2（一种与延伸中的RNA聚合酶II相关的组蛋白甲基转移酶）极为相似的表型。染色质免疫沉淀及生化实验表明，Eaf3的色域将Rpd3C(S)招募至组蛋白H3赖氨酸36处被Set2甲基化的核小体上，导致转录区域去乙酰化。此途径显然起到负向调节转录的作用，因为缺失Set2或Rpd3C(S)的基因可绕过对正向延伸因子Bur1/Bur2的需求。