MeCP2在Rett综合征中的调控机制

Regulation mechanism and research progress of MeCP2 in Rett syndrome

Rett综合征(Rett syndrome,RTT)是一种X连锁的神经发育障碍性遗传病,是导致女性严重智力障碍的主要原因之一。编码甲基化CpG结合蛋白2(Methyl-CpG-binding protein 2,MeCP2)基因突变是RTT主要的遗传病理学改变,MeCP2作为转录抑制因子调控基因表达。在RTT发病机制中,由于缺乏MeCP2与甲基化DNA的正确结合,阻碍了它对下游靶基因表达的正常调控,最终导致脑功能障碍。目前,对MeCP2在脑发育过程中的作用以及如何导致RTT的发生,其机制尚不清楚。文章从MECP2基因和MeCP2蛋白两个方面,对基因结构、蛋白质功能以及在分子水平上的调控机制进行了综述,以期为RTT的发病机制研究提供新思路。

Rett syndrome （RTT） is an X-linked neurodevelopmental disease accountable for some of the severe mental retardation of females. Mutations in the gene encoding mythyl-CpG-binding protein 2, MeCP2, which acts as a suppressor of gene expression, are the primary genetic pathological change of RTT. Insufficient binding of MeCP2 with methylated DNA disrupts the proper expression of target genes and results in brain dysfunction. Currently, the proper role MeCP2 played in the process of brain development and the occurrence of RTT remain elusive. In this review, we summarize both the MECP2 gene and MeCP2 protein, with highlight upon their structures, functions and more importantly their regulatory mechanisms at the molecular level so as to elucidate the mechanisms underlying the pathogenesis of RTT.