Figure 1. Vignettes of MeCP2 function. A, MeCP2 as a transcriptional repressor. MeCP2 binds to methylated CpG upstream of the transcriptional start site of a MeCP2 target gene. This recruits repressive cofactors to presumably cause local chromatin compaction and transcriptional downregulation. B, MeCP2 as a transcriptional activator. In this case, MeCP2 recruits a transcriptional coactivator to cause the transcriptional upregulation of a target gene. C, MeCP2 and histone H1. The regulation of repetitive elements and perhaps MeCP2 target gene expression may by coordinated by a dynamic interplay between MeCP2 and histone H1. D, MeCP2 and glia. A mutant MeCP2-expressing glial cell (Mecp2-mutant) may secrete a cytotoxic factor. This may be deleterious to the normal function(s) of wild-type MeCP2-expressing neurons (Mecp2-wt). E, MeCP2, and cell- and non-cell-autonomous mechanisms. Shown is one experimental example of how both cell- and non-cell-autonomous mechanisms are important in the manifestation of RTT phenotypes. The transplant experiments are described in the text. F, MeCP2, miRNAs, and drug addiction. miRNAs have an emerging role in the regulation of both Mecp2 and Bdnf, a MeCP2 target gene. Arrows and blocks indicate activation and repression, respectively. Recent evidence also demonstrates that MeCP2 and miR-212 play important roles in cocaine addiction.