Home LiteratureArticle Details
PMID: 7777532 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 12 ·1995-06-06 ·Pages 5465-9

Otten AD, Tapscott SJ

Abstract

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.

MeSH Terms
Adult Cells, Cultured Chromatin/chemistry DNA/metabolism Deoxyribonucleases Fibroblasts/metabolism Humans Muscle, Skeletal/cytology,metabolism Myotonic Dystrophy/genetics Protein Conformation Repetitive Sequences, Nucleic Acid
Chemicals
Chromatin DNA Deoxyribonucleases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Otten A D
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Tapscott S J
References (25)
25 references, click to expand
  1. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD.
    Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434-8 PMID: 2748593
  2. Preferential nucleosome assembly at DNA triplet repeats from the myotonic dystrophy gene.
    Science. 1994 Jul 29;265(5172):669-71 PMID: 8036515
  3. Proposed genetic basis of Huntington's disease.
    Trends Genet. 1990 Aug;6(8):242-7 PMID: 2146788
  4. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection.
    Science. 1990 Nov 23;250(4984):1104-10 PMID: 2174572
  5. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member.
    Cell. 1992 Feb 21;68(4):799-808 PMID: 1310900
  6. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy.
    Nature. 1992 Feb 6;355(6360):545-6 PMID: 1346923
  7. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene.
    Science. 1992 Mar 6;255(5049):1253-5 PMID: 1546325
  8. Triplet repeat mutations in human disease.
    Science. 1992 May 8;256(5058):784-9 PMID: 1589758
  9. Promoter sequence containing (CT)n.(GA)n repeats is critical for the formation of the DNase I hypersensitive sites in the Drosophila hsp26 gene.
    J Mol Biol. 1992 Jun 20;225(4):985-98 PMID: 1377279
  10. Minimal expression of myotonic dystrophy: a clinical and molecular analysis.
    J Med Genet. 1992 Nov;29(11):770-3 PMID: 1453424
  11. The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy.
    J Med Genet. 1992 Nov;29(11):774-9 PMID: 1453425
  12. Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy.
    Science. 1993 Apr 9;260(5105):235-8 PMID: 8469976
  13. A study of DNA methylation in myotonic dystrophy.
    J Med Genet. 1993 Mar;30(3):189-92 PMID: 8097255
  14. (CT)n (GA)n repeats and heat shock elements have distinct roles in chromatin structure and transcriptional activation of the Drosophila hsp26 gene.
    Mol Cell Biol. 1993 May;13(5):2802-14 PMID: 8474442
  15. Insertion/deletion polymorphism at D19S95 associated with the myotonic dystrophy CTG repeat.
    Hum Mol Genet. 1992 Sep;1(6):451 PMID: 1338761
  16. Characterization of the myotonic dystrophy region predicts multiple protein isoform-encoding mRNAs.
    Nat Genet. 1992 Jul;1(4):261-6 PMID: 1302022
  17. Failure in detecting mRNA transcripts from the mutated allele in myotonic dystrophy muscle.
    Biochem Mol Biol Int. 1993 Feb;29(2):291-7 PMID: 8495213
  18. Effect of the myotonic dystrophy (DM) mutation on mRNA levels of the DM gene.
    Nat Genet. 1993 Jul;4(3):233-8 PMID: 8358430
  19. Analysis of dystrophin expression after activation of myogenesis in amniocytes, chorionic-villus cells, and fibroblasts. A new method for diagnosing Duchenne's muscular dystrophy.
    N Engl J Med. 1993 Sep 23;329(13):915-20 PMID: 8361505
  20. Myotonic dystrophy: absence of CTG enlarged transcript in congenital forms, and low expression of the normal allele.
    Hum Mol Genet. 1993 Aug;2(8):1263-6 PMID: 7691346
  21. Absence of myotonic dystrophy protein kinase (DMPK) mRNA as a result of a triplet repeat expansion in myotonic dystrophy.
    Genomics. 1993 Nov;18(2):340-8 PMID: 8288237
  22. Genomic organization and transcriptional units at the myotonic dystrophy locus.
    Genomics. 1993 Dec;18(3):673-9 PMID: 7905855
  23. French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion.
    J Med Genet. 1994 Jan;31(1):33-6 PMID: 8151634
  24. High resolution genetic analysis suggests one ancestral predisposing haplotype for the origin of the myotonic dystrophy mutation.
    Hum Mol Genet. 1994 Jan;3(1):45-51 PMID: 7909252
  25. Trans-inactivation of the Drosophila brown gene: evidence for transcriptional repression and somatic pairing dependence.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6704-8 PMID: 2505257
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.12.5465
Published
1995-06-06
Pages
5465-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41715
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.12.5465 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2