The American Journal of Human Genetics, 1998, Vol.62(2), pp.278-285
Using methylation-sensitive restriction enzymes, we characterized the methylation pattern on the 5′ side of the CTG repeat in the DMPK gene of normal individuals and of patients affected with myotonic dystrophy, showing expansions of the repetitive sequence. The gene segment analyzed corresponds to the genomic I- dIII fragment carrying exons 11–15. There is constitutive methylation in intron 12 at restriction sites of II and I, localized 1,159–1,232 bp upstream of the CTG repeat, whereas most, if not all, of the other sites of II, I, and II in this region are unmethylated, in normal individuals and most of the patients. In a number of young and severely affected patients, however, complete methylation of these restriction sites was found in the mutated allele. In most of these patients, the onset of the disease was congenital. Preliminary in vivo footprinting data gave evidence for protein-DNA contact in normal genes at an Sp1 consensus binding site upstream of the CTG repeat and for a significant reduction of this interaction in cells with a hypermethylated DMPK gene.
Myotonic Dystrophy ; Dmpk Gene ; Ctg Repeat Expansion ; DNA Methylation ; in Vivo Footprinting ; Biology
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