Fragile X syndrome unstable element, p(CCG)n, and other simple tandem repeat sequences are binding sites for specific nuclear proteins

Abstract

The trinucleotide repeat sequences which become unstable In fraglle X syndrome and myotonic dystrophy are located In the untranslated regions of their respective genes, FMR1 and DM1. This lmplies that a functional constraint other than coding capacity maintains the presence of the repeats. In the case of fraglle X syndrome, sequences adjacent to the repeat are methylated In affected individuals and the FMR1 gene is transcriptionally Inactive. We demonstrate that the fraglle X p(CCG)n repeat Itself Is methylated In vivo and that methylation of this repeat Is able to Inhibit In vitro binding of a novel, specific nuclear p(CCG)n binding protein (CCG-BP1)-one of at least 10 distinct simple tandem 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.