Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure
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&...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1995-06, Vol.92 (12), p.5465-5469 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Otten, A D Tapscott, S J |
| description | 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. |
| doi_str_mv | 10.1073/pnas.92.12.5465 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.92.12.5465</identifier><identifier>PMID: 7777532</identifier><language>eng</language><publisher>United States: National Acad Sciences</publisher><subject>Adult ; Cells, Cultured ; chromatin ; Chromatin - chemistry ; Deoxyribonucleases ; Disease ; DNA - metabolism ; Fibroblasts - metabolism ; Genes ; Humans ; man ; Medical research ; Muscle, Skeletal - cytology ; Muscle, Skeletal - metabolism ; myotonic dystrophy ; Myotonic Dystrophy - genetics ; Protein Conformation ; Proteins ; Repetitive Sequences, Nucleic Acid</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1995-06, Vol.92 (12), p.5465-5469</ispartof><rights>Copyright National Academy of Sciences Jun 6, 1995</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-661dea91b8e7e416ed4d8bd41304e67ec2fabd322381f3da1a59e51111bdaf8c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/92/12.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC41715/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC41715/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7777532$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Otten, A D</creatorcontrib><creatorcontrib>Tapscott, S J</creatorcontrib><title>Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>Adult</subject><subject>Cells, Cultured</subject><subject>chromatin</subject><subject>Chromatin - chemistry</subject><subject>Deoxyribonucleases</subject><subject>Disease</subject><subject>DNA - metabolism</subject><subject>Fibroblasts - metabolism</subject><subject>Genes</subject><subject>Humans</subject><subject>man</subject><subject>Medical research</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>myotonic dystrophy</subject><subject>Myotonic Dystrophy - genetics</subject><subject>Protein Conformation</subject><subject>Proteins</subject><subject>Repetitive Sequences, Nucleic Acid</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS1EVZbCmRPI4gCnbP0VJ5a4oIqPSpW4FK6WY0_YrBI72A7q_vc46lLRHspc5vB-b2bsh9ArSraUNPx89iZtFdtStq2FrJ-gDSWKVlIo8hRtCGFN1QomnqHnKe0JIapuySk6bUrVnG3Qj-s4zCNkHGEGkzHczManIXg8eDwdQg5-sNgdUo5h3h2wGTPEhPMOsHF7Y8FnbHcxTCYXQ6EWm5cIL9BJb8YEL4_9DH3__On64mt19e3L5cXHq8oKpXIlJXVgFO1aaEBQCU64tnOCciJANmBZbzrHGeMt7bkz1NQKalqqc6ZvLT9DH27nzks3gVvPiWbUcxwmEw86mEHfV_yw0z_Dby1oQ-tif3e0x_BrgZT1NCQL42g8hCXppll3K_ZfkMpGCsl4Ad8-APdhib78gWaEcqFq1hbo_BayMaQUob87mBK9xqrXWLVimjK9xlocr_995x1_zLHob476avyr3hvw_lFA98tYor3J_A8-fLlN</recordid><startdate>19950606</startdate><enddate>19950606</enddate><creator>Otten, A D</creator><creator>Tapscott, S J</creator><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7T3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19950606</creationdate><title>Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure</title><author>Otten, A D ; Tapscott, S J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-661dea91b8e7e416ed4d8bd41304e67ec2fabd322381f3da1a59e51111bdaf8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Adult</topic><topic>Cells, Cultured</topic><topic>chromatin</topic><topic>Chromatin - chemistry</topic><topic>Deoxyribonucleases</topic><topic>Disease</topic><topic>DNA - metabolism</topic><topic>Fibroblasts - metabolism</topic><topic>Genes</topic><topic>Humans</topic><topic>man</topic><topic>Medical research</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>myotonic dystrophy</topic><topic>Myotonic Dystrophy - genetics</topic><topic>Protein Conformation</topic><topic>Proteins</topic><topic>Repetitive Sequences, Nucleic Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Otten, A D</creatorcontrib><creatorcontrib>Tapscott, S J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Human Genome Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Otten, A D</au><au>Tapscott, S J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1995-06-06</date><risdate>1995</risdate><volume>92</volume><issue>12</issue><spage>5465</spage><epage>5469</epage><pages>5465-5469</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><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. 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| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Cells, Cultured chromatin Chromatin - chemistry Deoxyribonucleases Disease DNA - metabolism Fibroblasts - metabolism Genes Humans man Medical research Muscle, Skeletal - cytology Muscle, Skeletal - metabolism myotonic dystrophy Myotonic Dystrophy - genetics Protein Conformation Proteins Repetitive Sequences, Nucleic Acid |
| title | Triplet repeat expansion in myotonic dystrophy alters the adjacent chromatin structure |
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