Doyen Cécile-Marie, An Woojin, Angelov Dimitar, Bondarenko Vladimir, Mietton Flore, Studitsky Vassily M, Hamiche Ali, Roeder Robert G, Bouvet Philippe, Dimitrov Stefan
Institut Albert Bonniot, INSERM U309, 38706 La Tronche cedex, France.
Mol Cell Biol. 2006 Feb;26(3):1156-64. doi: 10.1128/MCB.26.3.1156-1164.2006.
macroH2A (mH2A) is an unusual histone variant consisting of a histone H2A-like domain fused to a large nonhistone region. In this work, we show that histone mH2A represses p300- and Gal4-VP16-dependent polymerase II transcription, and we have dissected the mechanism by which this repression is realized. The repressive effect of mH2A is observed at the level of initiation but not at elongation of transcription, and mH2A interferes with p300-dependent histone acetylation. The nonhistone region of mH2A is responsible for both the repression of initiation of transcription and the inhibition of histone acetylation. In addition, the presence of this domain of mH2A within the nucleosome is able to block nucleosome remodeling and sliding of the histone octamer to neighboring DNA segments by the remodelers SWI/SNF and ACF. These data unambiguously identify mH2A as a strong transcriptional repressor and show that the repressive effect of mH2A is realized on at least two different transcription activation chromatin-dependent pathways: histone acetylation and nucleosome remodeling.
巨H2A（mH2A）是一种特殊的组蛋白变体，由一个与大的非组蛋白区域融合的类组蛋白H2A结构域组成。在这项研究中，我们发现组蛋白mH2A可抑制p300和Gal4-VP16依赖的聚合酶II转录，并且我们剖析了这种抑制作用实现的机制。mH2A的抑制作用在转录起始水平即可观察到，而在转录延伸阶段则未观察到，并且mH2A会干扰p300依赖的组蛋白乙酰化。mH2A的非组蛋白区域既负责转录起始的抑制，也负责组蛋白乙酰化的抑制。此外，核小体内mH2A的这个结构域能够通过重塑因子SWI/SNF和ACF阻止核小体重塑以及组蛋白八聚体向相邻DNA片段的滑动。这些数据明确地将mH2A鉴定为一种强效的转录抑制因子，并表明mH2A的抑制作用至少通过两种不同的转录激活染色质依赖途径实现：组蛋白乙酰化和核小体重塑。
