Mi-2β associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities
Mi-2β associates with BRG1 and RET finger protein at the distinct regions with transcriptional activating and repressing abilities
复制标题
DOI：
10.1074/jbc.m309198200
复制
发表时间：
2003-12-19
影响因子：
4.8
通讯作者：
Takahashi, M
中科院分区：
文献类型：
--
作者：
Shimono, Y;Murakami, H;Takahashi, M
Mi-2 β是核小体重塑和脱乙酰酶复合物的主要成分，在表观遗传转录抑制中起重要作用。在这里，我们发现Mi-2 β的氨基末端和羧基末端区域具有不同的转录活性，并分别与SWI/SNF复合物的组分BRG 1和RET指蛋白（RFP）结合。荧光素酶报告基因分析表明，Mi-2 β的氨基端区域具有较强的反式激活活性，羧基端区域具有转录抑制活性。Mi- 2、RFP和组蛋白去乙酰化酶1的共定位和关联表明这些蛋白质在转录抑制中合作。此外，通过使用RFP（-/-）成纤维细胞证实Mi-2 β和RFP结合的功能重要性。另一方面，我们证明Mi- 2和BRG 1相互关联，BRG 1的布罗莫结构域区域强烈抑制Mi-2 β氨基末端区域的反式激活。Mi-2 β与反式激活蛋白和抑制蛋白相互作用，并与另一种染色质重塑蛋白BRG 1直接相关，这一发现为参与转录调控的多蛋白超复合物的形成提供了新的见解。
Mi-2beta is the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Here we show that the amino-terminal and carboxyl-terminal regions of Mi-2beta have distinct transcriptional activities and bind to BRG1, a component of the SWI/SNF complex, and the RET finger protein (RFP), respectively. Analysis by luciferase reporter assay revealed that the amino-terminal region of Mi-2beta has a strong transactivating ability, whereas its carboxyl-terminal region has transcriptional repressive activity. Co-localization and association of Mi- 2, RFP, and histone deacetylase 1 suggested that these proteins cooperate in transcriptional repression. Furthermore, the functional importance of the association of Mi-2beta and RFP was confirmed by using Rfp(-/-) fibroblasts. On the other hand, we demonstrated that Mi- 2 and BRG1 were associated with each other and that the bromodomain region of BRG1 strongly suppressed transactivation by the amino-terminal region of Mi-2beta. The findings that Mi-2beta interacts with both transactivating and repressing proteins and directly associates with another chromatin remodeling protein, BRG1, provide new insight into the formation of multiprotein supercomplex involved in transcriptional regulation.