Abstract
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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites / physiology
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CCCTC-Binding Factor
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Cell Line
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Cell-Free System
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CpG Islands / genetics
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DNA Methylation*
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DNA-Binding Proteins / metabolism*
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Homeodomain Proteins / genetics
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Humans
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Molecular Sequence Data
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Myotonic Dystrophy / genetics*
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Myotonin-Protein Kinase
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Nuclear Matrix / metabolism
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Nucleosomes / metabolism
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Protein Serine-Threonine Kinases / genetics
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Repressor Proteins*
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Sequence Homology, Nucleic Acid
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Transcription Factors / metabolism*
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Trinucleotide Repeats / genetics*
Substances
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CCCTC-Binding Factor
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CTCF protein, human
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DMPK protein, human
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DNA-Binding Proteins
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Homeodomain Proteins
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Nucleosomes
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Repressor Proteins
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SIX5 protein, human
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Transcription Factors
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Myotonin-Protein Kinase
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Protein Serine-Threonine Kinases