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CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locusLobanenkov, 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
Nature genetics, 08/2001, Letnik: 28, Številka: 4Journal Article
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.
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