Figure 7.

Proposed model for VPA- and AMI- mediated epigenetic alterations in astrocytes. VPA and AMI display an input on global DNA demethylation, although through different mechanisms. As VPA inhibits HDACs, and AMI impairs DNMT function, the measurable difference in global epigenetic marks consists of hyperacetylation of histones in the case of VPA, which are not affected by AMI. Locally, downstream pathways further diverge as exemplified for the GLT-1 gene. The biochemical composition of the promoter is markedly altered by VPA exposure by means of histone hyperacetylation and DNA demethylation, resulting in an enhanced gene transcription. AMI does not possess similar features, and subsequently leaves gene activity unaffected. Round circles represent CpG sites; shading reflects the degree of methylation; oval circles depict core histones.