Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.
AUTOR(ES)
Otten, A D
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=41715Documentos Relacionados
- Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy.
- Expansion of the myotonic dystrophy gene in Italian and Spanish patients.
- Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.
- Instability in the normal CTG repeat range at the myotonic dystrophy locus.
- French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion.
