The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome (Retracted article. See vol. 149, pg. 245, 2012)
The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome (Retracted article. See vol. 149, pg. 245, 2012)
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DOI：
10.1016/s0092-8674(03)00436-7
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发表时间：
2003-06-27
期刊：
影响因子：
64.5
通讯作者：
Kato, S
中科院分区：
文献类型：
--
作者：
Kitagawa, H;Fujiki, R;Kato, S
我们鉴定了一种人多蛋白复合物（WINAC），它通过威廉姆斯综合征转录因子（WSTF）与维生素D受体（VDR）直接相互作用，WINAC具有ATP依赖的染色质重塑活性，同时含有SWI/SNF组分和DNA复制相关因子。后者可能解释了正常S期进展的WINAC要求。WINAC介导未配体的VDR募集到启动子中的VDR靶位点，而随后的辅调节因子的结合需要配体结合。这种招募顺序说明，序列特异性调节剂与染色质重塑复合物的相互作用可以在特定的局部位点组织核小体阵列，以使启动子可用于辅助调节剂。此外，WSTF的过表达可以恢复威廉姆斯综合征患者成纤维细胞中维生素D调节启动子对VDR的受损募集。这表明，WINAC功能障碍有助于威廉姆斯综合征，因此可以认为，至少部分，染色质重塑因子疾病。
We identified a human multiprotein complex (WINAC) that directly interacts with the vitamin D receptor (VDR) through the Williams syndrome transcription factor (WSTF), WINAC has ATP-dependent chromatin-remodeling activity and contains both SWI/SNF components and DNA replication-related factors. The latter might explain a WINAC requirement for normal S phase progression. WINAC mediates the recruitment of unliganded VDR to VDR target sites in promoters, while subsequent binding of coregulators requires ligand binding. This recruitment order exemplifies that an interaction of a sequence-specific regulator with a chromatin-remodeling complex can organize nucleosomal arrays at specific local sites in order to make promoters accessible for coregulators. Furthermore, overexpression of WSTF could restore the impaired recruitment of VDR to vitamin D regulated promoters in fibroblasts from Williams syndrome patients. This suggests that WINAC dysfunction contributes to Williams syndrome, which could therefore be considered, at least in part, a chromatin-remodeling factor disease.