Figure 2.

Schematic illustration of the mechanism and consequences of DNA methylation changes in Huntington’s disease (HD). Mutant Huntingtin (mHtt) directly or indirectly modulates the activities of transcriptional factors (TF), DNA methyltransferases (DNMT), and chromatin-modifying factors (CMF) that act in concert to alter the chromatin landscape, including DNA methylation. In HD altered DNA methylation occurs genome-wide and affects both transcriptional start site (TSS) proximal CpG islands (CGI) and intergenic CpG sites thereby influencing transcription regulation, stability of trinucleotide repeats, and mobile genetic elements, and epigenetic age.