组蛋白变体macroH2A会干扰转录因子结合以及SWI/SNF核小体重塑。

The histone variant macroH2A interferes with transcription factor binding and SWI/SNF nucleosome remodeling.

作者信息

Angelov Dimitar, Molla Annie, Perche Pierre-Yves, Hans Fabienne, Côté Jacques, Khochbin Saadi, Bouvet Philippe, Dimitrov Stefan

机构信息

Ecole Normale Supérieure de Lyon, CNRS-UMR 5665, 46 Allée d'Italie, France.

出版信息

Mol Cell. 2003 Apr;11(4):1033-41. doi: 10.1016/s1097-2765(03)00100-x.

DOI:10.1016/s1097-2765(03)00100-x

PMID:12718888

Abstract

The unusual histone variant macroH2A (mH2A) has been associated with repression of transcription, but the molecular mechanisms by which it exerts this function are unknown. Here we have identified a mechanism by which the different domains of mH2A may be involved in the repression of transcription. Evidence is presented that the presence of mH2A in a positioned nucleosome interferes with the binding of the transcription factor NF-kappaB. The nonhistone region of mH2A was identified to be associated with this interference. Importantly, the presence of macroH2A was found to severely impede SWI/SNF nucleosome remodeling and movement to neighboring DNA segments. This property of mH2A was demonstrated to reside only in its H2A-like domain. A hypothesis explaining the role of histone variants in transcriptional regulation is proposed.

摘要

异常组蛋白变体macroH2A（mH2A）与转录抑制有关，但其发挥该功能的分子机制尚不清楚。在此，我们确定了一种mH2A不同结构域可能参与转录抑制的机制。有证据表明，定位核小体中mH2A的存在会干扰转录因子NF-κB的结合。mH2A的非组蛋白区域被确定与这种干扰有关。重要的是，发现macroH2A的存在会严重阻碍SWI/SNF核小体重塑以及向相邻DNA片段的移动。mH2A的这一特性仅存在于其H2A样结构域中。我们提出了一个解释组蛋白变体在转录调控中作用的假说。