Instability and chromatin structure of expanded trinucleotide repeats.

Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. vincent.dion@fmi.ch

Trends in genetics : TIG 2009 Jul

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Trinucleotide repeat expansion underlies at least 17 neurological diseases. In affected individuals, the expanded locus is characterized by dramatic changes in chromatin structure and in repeat tract length. Interestingly, recent studies show that several chromatin modifiers, including a histone acetyltransferase, a DNA methyltransferase and the chromatin insulator CTCF can modulate repeat instability. Here, we propose that the unusual chromatin structure of expanded repeats directly impacts their instability. We discuss several potential models for how this might occur, including a role for DNA repair-dependent epigenetic reprogramming in increasing repeat instability, and the capacity of epigenetic marks to alter sense and antisense transcription, thereby affecting repeat instability.