CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus
An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element b...
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| Veröffentlicht in: | Nature genetics 2001-08, Vol.28 (4), p.335-343 |
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| container_title | Nature genetics |
| container_volume | 28 |
| creator | Lobanenkov, Victor V Tapscott, Stephen J Filippova, Galina N Thienes, Cortlandt P Penn, Bennett H Cho, Diane H Hu, Ying Jia Moore, James M Klesert, Todd R |
| description | An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome. |
| doi_str_mv | 10.1038/ng570 |
| format | Article |
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Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng570</identifier><identifier>PMID: 11479593</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>London: Nature Publishing Group</publisher><subject>Binding sites ; Binding Sites - physiology ; Biological and medical sciences ; CCCTC-Binding Factor ; Cell Line ; Cell-Free System ; Congenital diseases ; CpG Islands - genetics ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Disease ; DM1 gene ; DMPK gene ; DNA Methylation ; DNA-Binding Proteins - metabolism ; Dystrophy ; Gene expression ; Genes ; Genetic aspects ; Health aspects ; Homeodomain Proteins - genetics ; Humans ; Medical sciences ; Methylation ; Molecular Sequence Data ; Myotonic dystrophy ; Myotonic Dystrophy - genetics ; Myotonin-Protein Kinase ; Neurology ; Nuclear Matrix - metabolism ; Nucleosomes - metabolism ; Physiological aspects ; Polypeptides ; Protein-Serine-Threonine Kinases - genetics ; Publishing ; Repressor Proteins ; Risk factors ; Sequence Homology, Nucleic Acid ; SIX5 gene ; Transcription Factors - metabolism ; Trinucleotide Repeats - genetics</subject><ispartof>Nature genetics, 2001-08, Vol.28 (4), p.335-343</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c582t-a843f3c42d2eb1b68b72574bfbd95ba3d5e4b042814a2f117f4ee0fbd9c257653</citedby><cites>FETCH-LOGICAL-c582t-a843f3c42d2eb1b68b72574bfbd95ba3d5e4b042814a2f117f4ee0fbd9c257653</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14151496$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11479593$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lobanenkov, Victor V</creatorcontrib><creatorcontrib>Tapscott, Stephen J</creatorcontrib><creatorcontrib>Filippova, Galina N</creatorcontrib><creatorcontrib>Thienes, Cortlandt P</creatorcontrib><creatorcontrib>Penn, Bennett H</creatorcontrib><creatorcontrib>Cho, Diane H</creatorcontrib><creatorcontrib>Hu, Ying Jia</creatorcontrib><creatorcontrib>Moore, James M</creatorcontrib><creatorcontrib>Klesert, Todd R</creatorcontrib><title>CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><description>An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.</description><subject>Binding sites</subject><subject>Binding Sites - physiology</subject><subject>Biological and medical sciences</subject><subject>CCCTC-Binding Factor</subject><subject>Cell Line</subject><subject>Cell-Free System</subject><subject>Congenital diseases</subject><subject>CpG Islands - genetics</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Disease</subject><subject>DM1 gene</subject><subject>DMPK gene</subject><subject>DNA Methylation</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Dystrophy</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Homeodomain Proteins - genetics</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Methylation</subject><subject>Molecular Sequence Data</subject><subject>Myotonic dystrophy</subject><subject>Myotonic Dystrophy - genetics</subject><subject>Myotonin-Protein Kinase</subject><subject>Neurology</subject><subject>Nuclear Matrix - metabolism</subject><subject>Nucleosomes - metabolism</subject><subject>Physiological aspects</subject><subject>Polypeptides</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Publishing</subject><subject>Repressor Proteins</subject><subject>Risk factors</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>SIX5 gene</subject><subject>Transcription Factors - metabolism</subject><subject>Trinucleotide Repeats - genetics</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN0l-L1DAQAPAgineu9wkECYqCD73LNEn_PC7VWw9ODnT1taTtZC9nm-4lqXjf3tRdXFZ8kEASJr-ZJDCEnAE7B8aLC7uROXtETkGKLIEcisdxzzJIBOPZCXnm_R1jIAQrnpITAJGXsuSnpKvW1WXSGNsZu6HeBPRU98p-p9V6dVEtV9ThFlXwVNmO6tENVNEBw-1Dr4IZbeLRxizzA6mxforB0VEVaLhF-v4T0H5sJ_-cPNGq93i2Xxfk6-WHdfUxub5ZXVXL66SVRRoSVQiueSvSLsUGmqxo8lTmotFNV8pG8U6iaJhICxAq1QC5FohsPm2jyyRfkLe7uls33k_oQz0Y32If_4Pj5GsooOQgZ_jqL3g3Ts7Gt9VpmmZSCp5G9HqHNqrH2lg9BqfauWK9hIILns3Tgpz_Q8XR4WDa0aI2MX6U8O4oIZqAP8NGTd7XV18-_7-9-XZs3-xs60bvHep668yg3EMNrJ5bpP7dItG93P99agbsDmrfE4dCW-Vb1WunbGv8wQmQIMosuhc7Z1WYHP4Bu2t-AZqNx3k</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>Lobanenkov, Victor V</creator><creator>Tapscott, Stephen J</creator><creator>Filippova, Galina N</creator><creator>Thienes, Cortlandt P</creator><creator>Penn, Bennett H</creator><creator>Cho, Diane H</creator><creator>Hu, Ying Jia</creator><creator>Moore, James M</creator><creator>Klesert, Todd R</creator><general>Nature Publishing Group</general><scope>IQODW</scope><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20010801</creationdate><title>CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus</title><author>Lobanenkov, Victor V ; Tapscott, Stephen J ; Filippova, Galina N ; Thienes, Cortlandt P ; Penn, Bennett H ; Cho, Diane H ; Hu, Ying Jia ; Moore, James M ; Klesert, Todd R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c582t-a843f3c42d2eb1b68b72574bfbd95ba3d5e4b042814a2f117f4ee0fbd9c257653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Binding sites</topic><topic>Binding Sites - physiology</topic><topic>Biological and medical sciences</topic><topic>CCCTC-Binding Factor</topic><topic>Cell Line</topic><topic>Cell-Free System</topic><topic>Congenital diseases</topic><topic>CpG Islands - genetics</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. 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Prion diseases</topic><topic>Disease</topic><topic>DM1 gene</topic><topic>DMPK gene</topic><topic>DNA Methylation</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Dystrophy</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Homeodomain Proteins - genetics</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Methylation</topic><topic>Molecular Sequence Data</topic><topic>Myotonic dystrophy</topic><topic>Myotonic Dystrophy - genetics</topic><topic>Myotonin-Protein Kinase</topic><topic>Neurology</topic><topic>Nuclear Matrix - metabolism</topic><topic>Nucleosomes - metabolism</topic><topic>Physiological aspects</topic><topic>Polypeptides</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Publishing</topic><topic>Repressor Proteins</topic><topic>Risk factors</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>SIX5 gene</topic><topic>Transcription Factors - metabolism</topic><topic>Trinucleotide Repeats - 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Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome.</abstract><cop>London</cop><pub>Nature Publishing Group</pub><pmid>11479593</pmid><doi>10.1038/ng570</doi><tpages>9</tpages></addata></record> |
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| subjects | Binding sites Binding Sites - physiology Biological and medical sciences CCCTC-Binding Factor Cell Line Cell-Free System Congenital diseases CpG Islands - genetics Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease DM1 gene DMPK gene DNA Methylation DNA-Binding Proteins - metabolism Dystrophy Gene expression Genes Genetic aspects Health aspects Homeodomain Proteins - genetics Humans Medical sciences Methylation Molecular Sequence Data Myotonic dystrophy Myotonic Dystrophy - genetics Myotonin-Protein Kinase Neurology Nuclear Matrix - metabolism Nucleosomes - metabolism Physiological aspects Polypeptides Protein-Serine-Threonine Kinases - genetics Publishing Repressor Proteins Risk factors Sequence Homology, Nucleic Acid SIX5 gene Transcription Factors - metabolism Trinucleotide Repeats - genetics |
| title | CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus |
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