Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
Annu Rev Cell Dev Biol. 2011;27:631-52. doi: 10.1146/annurev-cellbio-092910-154121. Epub 2011 Jun 29.
Methyl-CpG binding protein 2 (MeCP2) was first identified in 1992 as a protein that binds specifically to methylated DNA. Mutations in the MECP2 gene were later found to be the cause of an autism spectrum disorder, Rett syndrome. Despite almost 20 years of research into the molecular mechanisms of MeCP2 function, many questions are yet to be answered conclusively. This review considers several key questions and attempts to evaluate the current state of evidence. For example, is MeCP2 just a methyl-CpG binding protein? Is it a multifunctional protein or primarily a transcriptional repressor? We also consider whether MeCP2, as a chromosome-binding protein, acts at specific sites within the genome or more globally, and in which cell types it is functionally important. Finally, we consider two alternative views of MeCP2 in the brain: as a regulator of brain development or as a factor that helps maintain neuronal/glial function.
甲基化 CpG 结合蛋白 2（MeCP2）于 1992 年首次被鉴定为一种特异性结合甲基化 DNA 的蛋白质。后来发现 MECP2 基因突变是一种自闭症谱系障碍、雷特综合征的病因。尽管对 MeCP2 功能的分子机制进行了近 20 年的研究，但仍有许多问题尚未得到明确解答。本综述考虑了几个关键问题，并试图评估当前的证据状况。例如，MeCP2 仅仅是一种甲基化 CpG 结合蛋白吗？它是一种多功能蛋白还是主要的转录抑制剂？我们还考虑了 MeCP2 作为染色体结合蛋白，是在基因组的特定位置发挥作用还是更广泛地发挥作用，以及它在哪些细胞类型中具有功能重要性。最后，我们考虑了 MeCP2 在大脑中的两种替代观点：作为大脑发育的调节剂或作为帮助维持神经元/神经胶质功能的因素。
