The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.

The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.
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B型染色质复制复合物通过促进最大依赖性C-MYC结合来调节RNA聚合酶III转录。

DOI:
10.1093/nar/gkv312
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发表时间:
2015-05-19
影响因子:
14.9
通讯作者:
Östlund Farrants AK
Östlund Farrants AK
中科院分区:
生物学2区
文献类型:
--
作者:
Sadeghifar F;Böhm S;Vintermist A;Östlund Farrants AK

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染色质重塑复合物B-WICH由William综合征转录因子、ATP酶SNF 2 h和核肌球蛋白组成,特异性激活5S rRNA和7SL基因的RNA聚合酶III转录。然而,其潜在机制尚不清楚。使用高分辨率MN步行,我们在这里证明,B-WICH改变染色质结构附近的5S rRNA和7SL RNA基因在RNA聚合酶III转录。B-WICH的作用是RNA聚合酶机制和调节因子c-Myc在5S rRNA和7SL RNA基因处结合所必需的。除了在5S基因的c-Myc结合位点,我们已经发现了一个新的c-Myc和最大结合位点的5S rDNA的基因间间隔区。此区域还包含一个由B-WICH重新建模的区域。我们证明了c-Myc以Max依赖的方式结合到这两个位点,从而通过乙酰化组蛋白H3激活转录。c-Myc和Max的新结合模式将5S rRNA的转录与Myc/Max/Mxd网络连接起来。由于B-WICH的行为之前,c-Myc和其他因素,我们提出了一个模型,其中的B-WICH复合物是必需的,以保持开放的染色质结构在这些RNA聚合酶III基因。这是结合其他调节因子的先决条件。
The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here that B-WICH changes the chromatin structure in the vicinity of the 5S rRNA and 7SL RNA genes during RNA polymerase III transcription. The action of B-WICH is required for the binding of the RNA polymerase machinery and the regulatory factors c-Myc at the 5S rRNA and 7SL RNA genes. In addition to the c-Myc binding site at the 5S genes, we have revealed a novel c-Myc and Max binding site in the intergenic spacer of the 5S rDNA. This region also contains a region remodelled by B-WICH. We demonstrate that c-Myc binds to both sites in a Max-dependent way, and thereby activate transcription by acetylating histone H3. The novel binding patterns of c-Myc and Max link transcription of 5S rRNA to the Myc/Max/Mxd network. Since B-WICH acts prior to c-Myc and other factors, we propose a model in which the B-WICH complex is required to maintain an open chromatin structure at these RNA polymerase III genes. This is a prerequisite for the binding of additional regulatory factors.