HMGA1 mediates the activation of the CRYAB promoter by BRG1
HMGA1 mediates the activation of the CRYAB promoter by BRG1
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DOI：
10.1089/dna.2007.0629
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发表时间：
2007-10-01
影响因子：
3.1
通讯作者：
Zhao, Keji
中科院分区：
文献类型：
--
作者：
Duncan, Beverly;Zhao, Keji
α-B-晶体蛋白（alpha B-Crystallin，α-B-Crystallin）是一种小分子热休克蛋白，参与多种细胞过程，如转录、分化和病理过程。它在脊椎动物眼透镜中以高水平表达，而在多种其他细胞类型中以低水平表达。我们以前确定了CRAAB作为染色质重塑SWI/SNF样Brg或hBrm相关因子（BAF）复合物的靶基因。在这份报告中，我们确定了一个30 bp的DNA元件介导的激活brahma相关基因1（BRG 1）的ESTAB。该BRG 1反应元件位于紧邻转录起始位点上游的定位核小体的边缘。在该区域内的AT-丰富的序列结合的高迁移率族AT-钩1（HMGA 1）蛋白在体外和体内。我们证明了HMGA 1靶序列和HMGA 1蛋白是BRG 1最大激活HMGA AB启动子所必需的。我们的数据表明，HMGA 1非组蛋白染色质蛋白，SWI/SNF染色质重塑复合物，和序列特异性转录因子共同作用，以调节ESTAB基因的表达。
alpha B-Crystallin (CRYAB) is a small heat-shock protein that is implicated in many cellular processes, such as transcription and differentiation, as well as pathologic process. It is expressed at high levels in vertebrate eye lens and at low levels in a variety of other cell types. We previously identified CRYAB as a target gene of the chromatin-remodeling SWI/SNF-like Brg or hBrm-associated factors (BAF) complexes. In this report, we identify a 30 bp DNA element required for mediating the activation of CRYAB by brahma-related gene 1 (BRG1). This BRG1-response element is located at the edge of a positioned nucleosome immediately upstream of the transcription initiation site. An AT-rich sequence within this region is bound by the high-mobility group AT-hook 1 (HMGA1) proteins in vitro and in vivo. We demonstrate that theHMGA1 target sequences and HMGA1 proteins are required for the maximal activation of the CRYAB promoter by BRG1. Our data indicate that HMGA1 nonhistone chromatin proteins, the SWI/SNF chromatin remodeling complexes, and sequence-specific transcription factors act together to regulate the expression of the CRYAB gene.