Document Detail


Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.
MedLine Citation:
PMID:  7777532     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A D Otten; S J Tapscott
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  92     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-07-12     Completed Date:  1995-07-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  5465-9     Citation Subset:  IM    
Affiliation:
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cells, Cultured
Chromatin / chemistry*
DNA / metabolism
Deoxyribonucleases
Fibroblasts / metabolism
Humans
Muscle, Skeletal / cytology,  metabolism
Myotonic Dystrophy / genetics*
Protein Conformation
Repetitive Sequences, Nucleic Acid*
Chemical
Reg. No./Substance:
0/Chromatin; 9007-49-2/DNA; EC 3.1.-/Deoxyribonucleases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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