Statistical Enrichment of Epigenetic States Around Triplet Repeats that Can Undergo Expansions

Alexandra Essebier, Patricia Vera Wolf, Minh Duc Cao, Bernard J. Carroll, Sureshkumar Balasubramanian and Mikael Bodén, Front. Neurosci., 08 March 2016 doi:10.3389/fnins.2016.00092

Friedreich ataxia (FRDA) is a loss-of-function disease caused by an expanded intronic GAA repeat in the Frataxin (FXN) gene, and in our analysis it displayed the greatest number of epigenetic marks in its distance profile. Based on our statistical analyses of epigenetic marks around the repeat, specific hypotheses can be drawn to address this transition. For example, this is consistent with the findings that suggest that the inhibitors of histone deacetylase increase FXN expression levels. It would be interesting to assess whether blocking histone methyl transferase to prevent H3K9ac and H3K27ac would promote the stability of the GAA repeat.