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肌醇多磷酸对ATP依赖的染色质重塑复合物的调节作用。

Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates.

作者信息

Shen Xuetong, Xiao Hua, Ranallo Ryan, Wu Wei-Hua, Wu Carl

机构信息

Laboratory of Molecular Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.

出版信息

Science. 2003 Jan 3;299(5603):112-4. doi: 10.1126/science.1078068. Epub 2002 Nov 14.

Abstract

Eukaryotes use adenosine triphosphate (ATP)-dependent chromatin-remodeling complexes to regulate gene expression. Here, we show that inositol polyphosphates can modulate the activities of several chromatin-remodeling complexes in vitro. Inositol hexakisphosphate (IP6) inhibits nucleosome mobilization by NURF, ISW2, and INO80 complexes. In contrast, nucleosome mobilization by the yeast SWI/SNF complex is stimulated by inositol tetrakisphosphate (IP4) and inositol pentakisphosphate (IP5). We demonstrate that mutations in genes encoding inositol polyphosphate kinases that produce IP4, IP5, and IP6 impair transcription in vivo. These results provide a link between inositol polyphosphates, chromatin remodeling, and gene expression.

摘要

真核生物利用依赖三磷酸腺苷(ATP)的染色质重塑复合物来调节基因表达。在此,我们表明肌醇多磷酸在体外可调节几种染色质重塑复合物的活性。肌醇六磷酸(IP6)抑制NURF、ISW2和INO80复合物介导的核小体移动。相反,肌醇四磷酸(IP4)和肌醇五磷酸(IP5)可刺激酵母SWI/SNF复合物介导的核小体移动。我们证明,编码产生IP4、IP5和IP6的肌醇多磷酸激酶的基因突变会损害体内转录。这些结果在肌醇多磷酸、染色质重塑和基因表达之间建立了联系。

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