The CTG triplet repeat expansion in myotonic dystrophy alters adjacent chromatin structure, establishing a region of condensed chromatin that obscures an adjacent DNase I hypersensitive site.
The expansion of the CTG triplet repeat in myotonic dystrophy alters adjacent chromatin structure, creating a condensed region that may repress gene transcription and contribute to the disease mechanism.
Myotonic dystrophy is caused by an expansion of a CTG triplet repeat sequence in the 3' noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. This report demonstrates that a DNase I hypersensitive site is positioned 3' of the triplet repeat in the wild-type allele in both fibroblasts and skeletal muscle cells. In three unrelated individuals with myotonic dystrophy that have large expansions of the triplet repeat, the allele with the triplet repeat expansion exhibited both overall DNase I resistance and inaccessibility of nucleases to the adjacent hypersensitive site. These results indicate that the triplet repeat expansion alters the adjacent chromatin structure, establishing a region of condensed chromatin, and suggests a molecular mechanism for myotonic dystrophy.
Otten et al. (Tue,) conducted a other in Myotonic dystrophy (n=4). CTG triplet repeat expansion vs. Wild-type allele was evaluated on DNase I hypersensitivity and chromatin structure adjacent to the triplet repeat. The CTG triplet repeat expansion in myotonic dystrophy alters adjacent chromatin structure, establishing a region of condensed chromatin that obscures an adjacent DNase I hypersensitive site.