Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors
Largest subunits of the human SWI/SNF chromatin-remodeling complex promote transcriptional activation by steroid hormone receptors
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DOI：
10.1074/jbc.m205961200
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发表时间：
2002-11-01
影响因子：
4.8
通讯作者：
Tanese, N
中科院分区：
文献类型：
--
作者：
Inoue, H;Furukawa, T;Tanese, N
哺乳动物 SWI/SNF 相关复合物通过利用 ATP 水解的能量重塑染色质来促进基因转录。这些复合物向启动子的募集仍然知之甚少，可能涉及组蛋白修饰或与位点特异性转录因子或其他辅因子的直接相互作用。在这里，我们报告了两个相关但不同的 cDNA 克隆 hOsa1 和 hOsa2 的分离，它们编码人类 SWI/SNF 的最大亚基。 hOsa1 与之前报道的 BAF250 相同，hOsa2 与 hOsa1 具有高度的序列相似性。质谱分析以及 hOsa1 或 hOsa2 特异性抗体的免疫印迹证明 SWI/SNF-A 中存在这两种蛋白，但从 HeLa 细胞纯化的相关多溴 BRG1 相关因子复合物中不存在。共沉淀研究表明 hOsal 和 hOsa2 通过 hOsa 的 C 末端结构域与 BRG1 和 hBRM 结合。我们在 hBRM 和 BRG1 中定义了多个与 hOsa C 末端相互作用的结构域。在培养的哺乳动物细胞中，hOsa1 和 hOsa2 刺激糖皮质激素、雌激素和雄激素受体的转录。对于C-末端结构域或对于缺乏ARID DNA结合结构域的hOsa2多肽，没有观察到糖皮质激素受体介导的激活。这些结果表明 hOsa1 和 hOsa2 参与促进类固醇激素受体的转录激活。
The mammalian SWI/SNF-related complexes facilitate gene transcription by remodeling chromatin using the energy of ATP hydrolysis. The recruitment of these complexes to promoters remains poorly understood and may involve histone modifications or direct interactions with site-specific transcription factors or other cofactors. Here we report the isolation of two related but distinct cDNA clones, hOsa1 and hOsa2, that encode the largest subunits of human SWI/SNF. hOsa1 is identical to previously reported BAF250, and hOsa2 shares a high degree of sequence similarity with hOsa1. Mass spectrometric analysis, and immunoblotting with antibodies specific to hOsa1 or hOsa2 demonstrate the presence of both proteins in SWI/SNF-A but not in the related polybromo-BRG1-associated factors complex purified from HeLa cells. Co-precipitation studies indicate that hOsal and hOsa2 associate with BRG1 and hBRM through the C-terminal domain of hOsa. We define multiple domains within hBRM and BRG1 that interact with the hOsa C terminus. In cultured mammalian cells, hOsa1 and hOsa2 stimulate transcription by the glucocorticoid, estrogen, and androgen receptors. The glucocorticoid receptor-mediated activation is not observed with the C-terminal domain or with the hOsa2 polypeptide lacking the ARID DNA binding domain. These results suggest that hOsa1 and hOsa2 participate in promoting transcriptional activation by the steroid hormone receptors.