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Ssn6-Tup1与抑制所需的I类组蛋白去乙酰化酶相互作用。

Ssn6-Tup1 interacts with class I histone deacetylases required for repression.

作者信息

Watson A D, Edmondson D G, Bone J R, Mukai Y, Yu Y, Du W, Stillman D J, Roth S Y

机构信息

Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

出版信息

Genes Dev. 2000 Nov 1;14(21):2737-44. doi: 10.1101/gad.829100.

Abstract

Ssn6-Tup1 regulates multiple genes in yeast, providing a paradigm for corepressor functions. Tup1 interacts directly with histones H3 and H4, and mutation of these histones synergistically compromises Ssn6-Tup1-mediated repression. In vitro, Tup1 interacts preferentially with underacetylated isoforms of H3 and H4, suggesting that histone acetylation may modulate Tup1 functions in vivo. Here we report that histone hyperacetylation caused by combined mutations in genes encoding the histone deacetylases (HDACs) Rpd3, Hos1, and Hos2 abolishes Ssn6-Tup1 repression. Unlike HDAC mutations that do not affect repression, this combination of mutations causes concomitant hyperacetylation of both H3 and H4. Strikingly, two of these class I HDACs interact physically with Ssn6-Tup1. These findings suggest that Ssn6-Tup1 actively recruits deacetylase activities to deacetylate adjacent nucleosomes and promote Tup1-histone interactions.

摘要

Ssn6-Tup1调控酵母中的多个基因,为共抑制因子功能提供了一个范例。Tup1直接与组蛋白H3和H4相互作用,这些组蛋白的突变会协同损害Ssn6-Tup1介导的抑制作用。在体外,Tup1优先与H3和H4的低乙酰化异构体相互作用,这表明组蛋白乙酰化可能在体内调节Tup1的功能。在此我们报告,由编码组蛋白去乙酰化酶(HDAC)Rpd3、Hos1和Hos2的基因联合突变导致的组蛋白高度乙酰化消除了Ssn6-Tup1的抑制作用。与不影响抑制作用的HDAC突变不同,这种突变组合会导致H3和H4同时发生高度乙酰化。引人注目的是,这些I类HDAC中的两个与Ssn6-Tup1发生物理相互作用。这些发现表明,Ssn6-Tup1会主动募集去乙酰化酶活性,使相邻核小体去乙酰化,并促进Tup1与组蛋白的相互作用。

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