Zhou Jiansheng, Fan Jun Y, Rangasamy Danny, Tremethick David J
The John Curtin School of Medical Research, The Australian National University, PO Box 334, Canberra, Australian Capital Territory 2601, Australia.
Nat Struct Mol Biol. 2007 Nov;14(11):1070-6. doi: 10.1038/nsmb1323. Epub 2007 Oct 28.
Although it is believed that the interconversion between permissive and refractory chromatin structures is important in regulating gene transcription, this process is poorly understood. Central to addressing this issue is to elucidate how a nucleosomal array folds into higher-order chromatin structures. Such findings can then provide new insights into how the folding process is regulated to yield different functional states. Using well-defined in vitro chromatin-assembly and transcription systems, we show that a small acidic region on the surface of the nucleosome is crucial both for the folding of a nucleosomal template into the 30-nm chromatin fiber and for the efficient repression of transcription, thereby providing a mechanistic link between these two essential processes. This structure-function relationship has been exploited by complex eukaryotic cells through the replacement of H2A with the specific variant H2A.Bbd, which naturally lacks an acidic patch.
尽管人们认为允许性和难接近性染色质结构之间的相互转换在调节基因转录中很重要,但这一过程却知之甚少。解决这个问题的核心是阐明核小体阵列如何折叠成高阶染色质结构。这样的发现能够为折叠过程如何被调控以产生不同功能状态提供新的见解。利用定义明确的体外染色质组装和转录系统,我们发现核小体表面的一个小酸性区域对于核小体模板折叠成30纳米染色质纤维以及有效抑制转录都至关重要,从而在这两个基本过程之间建立了一种机制联系。复杂的真核细胞通过用天然缺乏酸性斑块的特定变体H2A.Bbd取代H2A,利用了这种结构 - 功能关系。