着丝粒异染色质建立和维持需求的功能分离

Functional separation of the requirements for establishment and maintenance of centromeric heterochromatin.

作者信息

Partridge Janet F, DeBeauchamp Jennifer L, Kosinski Aaron M, Ulrich Dagny L, Hadler Michael J, Noffsinger Victoria J P

机构信息

Department of Biochemistry, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.

出版信息

Mol Cell. 2007 May 25;26(4):593-602. doi: 10.1016/j.molcel.2007.05.004.

DOI:10.1016/j.molcel.2007.05.004

PMID:17531816

Abstract

The establishment and maintenance of centromeric heterochromatin in fission yeast require the RITS complex. Comprised of centromeric siRNAs, the chromodomain protein Chp1, Argonaute (Ago1), and Tas3, RITS couples the cellular RNAi pathway with assembly of constitutive heterochromatin. However, the mechanisms governing RITS-dependent establishment versus maintenance of centromeric heterochromatin remain unresolved. Here, we report that a mutant Tas3 protein that cannot bind Ago1 supports the maintenance of centromeric heterochromatin but cannot mediate efficient de novo establishment from cells transiently depleted for the histone H3 lysine 9 methyltransferase Clr4. In contrast, centromeric heterochromatin efficiently assembles in mutant cells transiently depleted for dicer. This mutant therefore allows ordering of the events leading to establishment of centromeric heterochromatin and places lysine 9 methylation of histone H3 upstream of dicer function.

摘要

裂殖酵母中着丝粒异染色质的建立和维持需要RITS复合物。RITS由着丝粒小干扰RNA、染色体结构域蛋白Chp1、AGO蛋白（Ago1）和Tas3组成，它将细胞RNA干扰途径与组成型异染色质的组装联系起来。然而，控制着丝粒异染色质依赖RITS建立和维持的机制仍未明确。在此，我们报道一种不能结合Ago1的突变型Tas3蛋白能够支持着丝粒异染色质的维持，但不能介导从瞬时缺失组蛋白H3赖氨酸9甲基转移酶Clr4的细胞中高效从头建立。相反，在瞬时缺失Dicer的突变细胞中，着丝粒异染色质能有效组装。因此，这种突变体能够确定导致着丝粒异染色质建立的事件顺序，并将组蛋白H3赖氨酸9甲基化置于Dicer功能的上游。