Nan X, Cross S, Bird A
Institute of Cell and Molecular Biology, University of Edinburgh, UK.
Novartis Found Symp. 1998;214:6-16; discussion 16-21, 46-50. doi: 10.1002/9780470515501.ch2.
An important consequence of CpG methylation is the local silencing of gene expression. In part this can be mediated by direct interference of methylation with the binding of transcription factors. The major component of silencing, however, appears to be the binding of repressors that have an affinity for methyl-CpG. We have studied two proteins that bind to methylated DNA, methyl-CpG-binding protein 1 (MeCP1) and MeCP2. MeCP2 is a relatively abundant chromosomal protein whose localization in the nucleus is primarily dependent on CpG methylation. We find that MeCP2 is a potent transcriptional repressor with a genome-wide distribution. MeCP1 requires multiple methylated CpGs for binding and has previously been implicated as a methyl-CpG-dependent transcriptional repressor. Recent cloning of a candidate gene for a component of MeCP1 may provide clues to its mechanism of action.
CpG甲基化的一个重要后果是基因表达的局部沉默。部分原因可能是甲基化直接干扰转录因子的结合。然而，沉默的主要成分似乎是与甲基化CpG具有亲和力的阻遏物的结合。我们研究了两种与甲基化DNA结合的蛋白质，甲基化CpG结合蛋白1（MeCP1）和MeCP2。MeCP2是一种相对丰富的染色体蛋白，其在细胞核中的定位主要取决于CpG甲基化。我们发现MeCP2是一种具有全基因组分布的强效转录阻遏物。MeCP1需要多个甲基化的CpG才能结合，并且先前被认为是一种依赖甲基化CpG的转录阻遏物。最近克隆的MeCP1一个成分的候选基因可能为其作用机制提供线索。
