Varga-Weisz P D, Wilm M, Bonte E, Dumas K, Mann M, Becker P B
European Molecular Biology Laboratory, Heidelberg, Germany.
Nature. 1997 Aug 7;388(6642):598-602. doi: 10.1038/41587.
Repressive chromatin structures need to be unravelled to allow DNA-binding proteins access to their target sequences. This de-repression constitutes an important point at which transcription and presumably other nuclear processes can be regulated. Energy-consuming enzyme complexes that facilitate the interaction of transcription factors with chromatin by modifying nucleosome structure are involved in this regulation. One such factor, nucleosome-remodelling factor (NURF), has been isolated from Drosophila embryo extracts. We have now identified a chromatin-accessibility complex (CHRAC) which uses energy to increase the general accessibility of DNA in chromatin. However, unlike other known chromatin remodelling factors, CHRAC can also function during chromatin assembly: it uses ATP to convert irregular chromatin into a regular array of nucleosomes with even spacing. CHRAC combines enzymes that modulate nucleosome structure and DNA topology. Using mass spectrometry, we identified two of the five CHRAC subunits as the ATPase ISWI, which is also part of NURF, and topoisomerase II. The presence of ISWI in different contexts suggests that chromatin remodelling machines have a modular nature and that ISWI has a central role in different chromatin remodelling reactions.
抑制性染色质结构需要解开，以便DNA结合蛋白能够接触到它们的靶序列。这种去抑制作用构成了一个重要的调控点，转录以及其他可能的核过程都可以在此处得到调控。通过修饰核小体结构来促进转录因子与染色质相互作用的耗能酶复合物参与了这一调控过程。其中一个这样的因子，核小体重塑因子（NURF），已从果蝇胚胎提取物中分离出来。我们现在鉴定出了一种染色质可及性复合物（CHRAC），它利用能量来增加染色质中DNA的整体可及性。然而，与其他已知的染色质重塑因子不同，CHRAC在染色质组装过程中也能发挥作用：它利用ATP将不规则的染色质转化为具有均匀间距的规则核小体阵列。CHRAC结合了调节核小体结构和DNA拓扑结构的酶。通过质谱分析，我们确定了五个CHRAC亚基中的两个为ATP酶ISWI（它也是NURF的一部分）和拓扑异构酶II。ISWI在不同环境中的存在表明染色质重塑机器具有模块化性质，并且ISWI在不同的染色质重塑反应中起着核心作用。
