[Research progress of Rett syndrome causing gene MECP2--the structure, function and modulation of MECP2]

Rett syndrome (RTT), an X-linked dominant neurodevelopmental disorder characterized by regression of language, stereotype hand movement and loss of purposeful hand use, is primarily caused by mutation of menthyl-CpG-binding protein 2 (MECP2). The 76 kb human MECP2 is characterized by three salient features: a very large intron 2 (60 kb), an 8.5 kb 3'-UTR with highly conserved regions and different polyadenylation sites, and a 40 kb intergenic region separating MECP2 from the nearest upstream gene. There are two isoforms of MeCP2, MeCP2e1 and MeCP2e2. The differences between the two isoforms, the function of the 3'-UTR and the long-range cis-regulatory sequences in the intergenic region were extensively studied. In contrast to initial report, recent studies show that MeCP2 binds not only to methylated promoters and silence transcription, but also to the sites outside of genes containing only a few of CpG islands. Furthermore, MeCP2 can function as both an activator and a repressor of transcription.