DNA促使组蛋白H2A和H2B在一个可诱导启动子处发生置换。

DNA instructed displacement of histones H2A and H2B at an inducible promoter.

作者信息

Vicent Guillermo P, Nacht A Silvina, Smith Corey L, Peterson Craig L, Dimitrov Stefan, Beato Miguel

机构信息

Centre de Regulació Genòmica, Universitat Pompeu Fabra, Passeig Marítim 37-49, E-08003 Barcelona, Spain.

出版信息

Mol Cell. 2004 Nov 5;16(3):439-52. doi: 10.1016/j.molcel.2004.10.025.

DOI:10.1016/j.molcel.2004.10.025

PMID:15525516

Abstract

Regulation of gene expression requires dynamic changes in chromatin, but the nature of these changes is not well understood. Here, we show that progesterone treatment of cultured cells leads to recruitment of progesterone receptor (PR) and SWI/SNF-related complexes to Mouse Mammary Tumor Virus (MMTV) promoter, accompanied by displacement of histones H2A and H2B from the nucleosome containing the receptor binding sites, but not from adjacent nucleosomes. PR recruits SWI/SNF to MMTV nucleosomes in vitro and facilitates synergistic binding of receptors and nuclear factor 1 to the promoter. In nucleosomes assembled on MMTV or mouse rDNA promoter sequences, SWI/SNF catalyzes ATP-dependent sliding of the histone octamer followed only on the MMTV promoter by displacement of histones H2A and H2B. In MMTV nucleosome arrays, SWI/SNF displaces H2A and H2B from nucleosome B and not from the adjacent nucleosome. Thus, the outcome of nucleosome remodeling by SWI/SNF depends on DNA sequence.

摘要

基因表达的调控需要染色质发生动态变化，但其变化的本质尚未完全清楚。在此，我们表明，用孕酮处理培养细胞会导致孕酮受体（PR）和SWI/SNF相关复合物被招募到小鼠乳腺肿瘤病毒（MMTV）启动子上，同时组蛋白H2A和H2B从含有受体结合位点的核小体上被置换下来，但相邻核小体上的组蛋白并未被置换。PR在体外将SWI/SNF招募到MMTV核小体上，并促进受体与核因子1协同结合到启动子上。在MMTV或小鼠核糖体DNA启动子序列组装的核小体中，SWI/SNF催化组蛋白八聚体的ATP依赖性滑动，随后仅在MMTV启动子上发生组蛋白H2A和H2B的置换。在MMTV核小体阵列中，SWI/SNF从核小体B上置换H2A和H2B，而不是从相邻核小体上置换。因此，SWI/SNF介导的核小体重塑的结果取决于DNA序列。