Fig. 5.

Proposed mechanism by which mouse RELN promoter hypermethylation and recruitment of chromatin remodeling complexes (MeCP2, HDACs, and corepressors) regulate reelin gene expression. The mouse reelin (RELN) promoter region depicted here is that reported by Tremolizzo et al. (39). Vertical bars represent CpG dinucleotides present in this region. Pink dots denote 5mC present in the sequence. Note the increase of 5mC in MET (methionine)-treated mice and the prevention of this increase in MET plus VPA (valproate)-treated mice. MeCP2 recruits corepressor complexes including HDACs and induces a state of gene repression. VPA induces loss of MeCP2 binding to the promoter and enhances transcription.