The methyl-CpG-binding protein MeCP2 and neurological disease
The methyl-CpG-binding protein MeCP2 and neurological disease
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DOI：
10.1042/bst0360575
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发表时间：
2008-08-01
影响因子：
3.9
通讯作者：
Bird, Adrian
中科院分区：
文献类型：
--
作者：
Bird, Adrian
甲基-CpG结合蛋白MeCP 2是在15年前发现的，作为寻找选择性结合甲基化DNA的蛋白质的一部分。它是一种核蛋白，主要与染色质结合，并在体内强烈偏好与甲基化DNA序列结合。来自模型系统的证据表明，MeCP 2可以将Sin 3a辅阻遏物复合物募集到启动子，导致转录抑制，因此表明MeCP 2可以解释DNA甲基化信号，从而导致基因沉默。人类MECP 2基因突变导致自闭症谱系障碍Rett综合征。MeCP 2在神经元中表达最高，缺乏这种蛋白质的小鼠表现出与Rett患者惊人相似的症状。令人惊讶的是，这些症状可以通过延迟激活“停止”的Mecp 2基因来有效逆转，这增加了人类Rett综合征也可能是可逆的希望。MeCP 2的未来研究有望揭示脑功能，神经疾病和DNA甲基化的生物学。
The methyl-CpG-binding protein MeCP2 was discovered over 15 years ago as part of a search for proteins that selectively bind methylated DNA. It is a nuclear protein that is largely chromatin-bound and has a strong preference for binding to methylated DNA sequences in vivo. Evidence from model systems shows that MeCP2 can recruit the Sin3a co-repressor complex to promoters leading to transcriptional repression, therefore suggesting that MeCP2 can interpret the DNA methylation signal to bring about gene silencing. Mutations in the human MECP2 gene cause the autism spectrum disorder Rett Syndrome. MeCP2 is most highly expressed in neurons, and mice lacking this protein show symptoms that strikingly parallel those of Rett patients. Surprisingly, these symptoms are efficiently reversed by delayed activation of a 'stopped' Mecp2 gene, raising hopes that human Rett syndrome may also be reversible. Future studies of MeCP2 promise to shed light upon brain function, neurological disease and the biology of DNA methylation.