布拉马蛋白将SWI/SNF染色质重塑复合体与MeCP2依赖的转录沉默联系起来。

Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing.

作者信息

Harikrishnan K N, Chow Maggie Z, Baker Emma K, Pal Sharmistha, Bassal Sahar, Brasacchio Daniella, Wang Li, Craig Jeff M, Jones Peter L, Sif Saïd, El-Osta Assam

机构信息

The Alfred Medical Research and Education Precinct, Baker Medical Research Institute, Epigenetics in Human Health and Disease Laboratory, Second Floor, Commercial Road, Prahran, Victoria 3181, Australia.

出版信息

Nat Genet. 2005 Mar;37(3):254-64. doi: 10.1038/ng1516. Epub 2005 Feb 6.

DOI:10.1038/ng1516

PMID:15696166

Abstract

Transcriptional repression of methylated genes can be mediated by the methyl-CpG binding protein MeCP2. Here we show that human Brahma (Brm), a catalytic component of the SWI/SNF-related chromatin-remodeling complex, associates with MeCP2 in vivo and is functionally linked with repression. We used a number of different molecular approaches and chromatin immunoprecipitation strategies to show a unique cooperation between Brm, BAF57 and MeCP2. We show that Brm and MeCP2 assembly on chromatin occurs on methylated genes in cancer and the gene FMR1 in fragile X syndrome. These experimental findings identify a new role for SWI/SNF in gene repression by MeCP2.

摘要

甲基化基因的转录抑制可由甲基化CpG结合蛋白MeCP2介导。在此我们表明，人Brahma（Brm）是SWI/SNF相关染色质重塑复合体的催化成分，在体内与MeCP2相互作用，且在功能上与基因抑制相关。我们使用了多种不同的分子方法和染色质免疫沉淀策略，以展示Brm、BAF57和MeCP2之间独特的协同作用。我们表明，Brm和MeCP2在染色质上的组装发生在癌症中的甲基化基因以及脆性X综合征中的FMR1基因上。这些实验结果确定了SWI/SNF在MeCP2介导的基因抑制中的新作用。