Epigenetic modifications in trinucleotide repeat diseases

Trends Mol Med. 2013 Nov;19(11):655-63. doi: 10.1016/j.molmed.2013.07.007. Epub 2013 Aug 14.


Accumulating evidence supports the important role for epigenetic changes in modulating clinical parameters of complex disorders, including neurodegenerative disease. Several conditions, including fragile X syndrome and Huntington's disease are caused by trinucleotide repeat (TNR) expansions in or near specific genes. Highlighting the link between epigenetic disruption and disease phenotype, recent studies have established significant correlations between clinical features, expansion size, gene expression, the chromatin profile, and DNA methylation in regions surrounding the TNR. Given the debilitating and sometimes fatal consequences of TNR disorders, understanding how an altered epigenetic profile impacts clinical outcome warrants further attention, and could provide key insights for developing novel epigenetic therapies and biomarkers. This review presents the current evidence of epigenetic changes in several TNR diseases.

Keywords: DNA expansions; DNA methylation; histone modification; neurodegenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease / genetics*
  • Epigenesis, Genetic*
  • Humans
  • Trinucleotide Repeat Expansion*