MeCP2 behaves as an elongated monomer that does not stably associate with the Sin3a chromatin remodeling complex
MeCP2 behaves as an elongated monomer that does not stably associate with the Sin3a chromatin remodeling complex
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DOI：
10.1074/jbc.m408284200
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发表时间：
2004-11-05
影响因子：
4.8
通讯作者：
Bird, AP
中科院分区：
文献类型：
--
作者：
Klose, RJ;Bird, AP
MeCP 2是一种转录因子，其识别并结合对称甲基化的CpG二核苷酸以抑制转录。MeCP 2可以与Sin 3a/组蛋白去乙酰化酶辅阻遏物复合物结合，并以组蛋白去乙酰化酶依赖的方式介导阻遏。在啮齿动物组织，培养细胞和非洲爪蟾卵母细胞的提取物中，我们发现，只有少量的哺乳动物MeCP 2与Sin 3a相互作用，这种相互作用是不稳定的。大鼠脑MeCP 2（53 kDa）的纯化表明没有相关蛋白，尽管通过尺寸排阻色谱法的表观分子量为400-500 kDa。生物物理分析表明，大的表观尺寸不是因为同源多聚化，因为MeCP 2始终表现为具有细长形状的单体蛋白。我们的研究结果表明，MeCP 2不是Sin 3a辅阻遏物复合物的专性组分，因此可能参与更多样化的辅因子的阻遏功能。
MeCP2 is a transcription factor that recognizes and binds symmetrically methylated CpG dinucleotides to repress transcription. MeCP2 can associate with the Sin3a/histone deacetylase corepressor complex and mediate repression in a histone deacetylase-dependent manner. In extracts from rodent tissues, cultured cells, and Xenopus laevis oocytes, we find that only a small amount of mammalian MeCP2 interacts with Sin3a and that this interaction is not stable. Purification of rat brain MeCP2 (53 kDa) indicates no associated proteins despite an apparent molecular mass by size exclusion chromatography of 400-500 kDa. Biophysical analysis demonstrated that the large apparent size was not because of homo-multimerization, as MeCP2 consistently behaves as a monomeric protein that has an elongated shape. Our findings indicate the MeCP2 is not an obligate component of the Sin3a corepressor complex and may therefore engage a more diverse range of cofactors for repressive function.