Epigenetics in Friedreich's Ataxia: Challenges and Opportunities for Therapy
Figure 2
The FXN chromatin organization in normal individuals and FRDA patients. (a) In normal individuals, the promoter contains H3K4me3 and H3K36me3, while downstream regions contain H3K79me2 and H3K36me3, marks for transcription initiation and elongation, respectively. All regions contain H3K9ac, a mark for active open chromatin. There is CTCF binding at the 5′-UTR. (b) In FRDA, depletion of CTCF may trigger the FAST-1 antisense transcription that may lead to the deacetylation of histones and the increase of H3K9me3 at the promoter and other regions of the gene. However, the levels of H3K4me3 and H3K36me3 are not substantially changed at the promoter (indicated by brackets), suggesting that there may be little deficiency of transcription initiation. The repressive histone marks, H3K27me3, H4K20me3 and H3K9me3, are observed throughout the gene, but most prominently at the upstream GAA repeat region, along with an increased DNA methylation. There are also reduced levels of H3K36me3 and H3K79me2 at the upstream GAA region, indicative of a defect of transcription elongation in FRDA.
