TRIPLET REPEAT EXPANSION IN MYOTONIC-DYSTROPHY ALTERS THE ADJACENT CHROMATIN STRUCTURE

被引:146
作者
OTTEN, AD
TAPSCOTT, SJ
机构
[1] Clinical Research Division, Fred Hutchinson Cancer Res. Center, Seattle, WA 98104
关键词
D O I
10.1073/pnas.92.12.5465
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Myotonic dystrophy is caused by an expansion of a CTG triplet repeat sequence in the 3' noncoding region of a protein kinase gene, get 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.
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页码:5465 / 5469
页数:5
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