FRAGILE-X SYNDROME UNSTABLE ELEMENT, P(CCG)N, AND OTHER SIMPLE TANDEMREPEAT SEQUENCES ARE BINDING-SITES FOR SPECIFIC NUCLEAR PROTEINS

The trinucleotide repeat sequences which become unstable in fragile X syndrome and myotonic dystrophy are located in the untranslated region s of their respective genes, FMR1 and DM1. This implies that a functio nal constraint other than coding capacity maintains the presence of th e repeats. In the case of fragile X syndrome, sequences adjacent to th e repeat are methylated in affected individuals and the FMR1 gene is t ranscriptionally inactive. We demonstrate that the fragile X p(CCG)n r epeat itself is methylated in vivo and that methylation of this repeat is able to inhibit in vitro binding of a novel, specific nuclear p(CC G)n binding protein (CCG-BP1) -one of at least 10 distinct simple tand em repeat sequence binding proteins (STR-BPs). We describe additional, apparently distinct, binding activities both for the methylated form of the p(CCG)n repeat and for each of the single strands of the repeat .