Wade P A
Emory University, Department of Pathology and Laboratory Medicine, Woodruff Memorial Research Building Room 7105B, 1639 Pierce Drive, Atlanta, GA 30322, USA.
Bioessays. 2001 Dec;23(12):1131-7. doi: 10.1002/bies.10008.
Since its discovery, methylation of DNA in mammalian cells has been correlated with transcriptional repression and with specialized chromatin structures. Recently, considerable progress has been reported in the identification of protein factors with a highly conserved DNA interaction surface, termed the methyl CpG-binding domain or MBD. A subset has been biochemically linked to histone deacetylases, suggesting a molecular mechanism for the functional properties of methylated DNA. Despite several obvious attractions, the connection between MBD proteins and histone deacetylases fails to explain all the existing data. In fact, the biochemistry and DNA-binding properties of most MBD family members have not been adequately described and considerable evidence exists for alternative mechanisms in the repression of methylated loci. Null mutations have been generated in mice for several MBD family members, the phenotypes of the mutant animals raise important questions regarding the functions of the MBD family. Here, I review the biochemistry, DNA-binding properties, and genetics of the MBD proteins that are linked to transcriptional repression, namely, MeCP2, MBD1, MBD2, and MBD3. Several models to account for the functional properties of methylated DNA are presented.
自DNA甲基化在哺乳动物细胞中被发现以来，它一直与转录抑制以及特殊的染色质结构相关。最近，在鉴定具有高度保守的DNA相互作用表面的蛋白质因子方面取得了显著进展，这些蛋白质因子被称为甲基化CpG结合结构域或MBD。其中一部分已在生物化学上与组蛋白脱乙酰酶联系起来，这为甲基化DNA的功能特性提供了一种分子机制。尽管有几个明显吸引人的地方，但MBD蛋白与组蛋白脱乙酰酶之间的联系并不能解释所有现有数据。事实上，大多数MBD家族成员的生物化学和DNA结合特性尚未得到充分描述，并且有大量证据表明在甲基化位点的抑制中存在其他机制。已在小鼠中产生了几种MBD家族成员的无效突变，突变动物的表型引发了关于MBD家族功能的重要问题。在这里，我将综述与转录抑制相关的MBD蛋白，即MeCP2、MBD1、MBD2和MBD3的生物化学、DNA结合特性和遗传学。文中还提出了几种解释甲基化DNA功能特性的模型。
