Fragile X syndrome unstable element, p(CCG)n, and other simple tandem repeat 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 regions of their respective genes, FMR1 and DM1. This implies that a functional constraint other than coding capacity maintains the presence of the repeats. In the case of fragile X syndrome, sequences adjacent to the repeat are methylated in affected individuals and the FMR1 gene is transcriptionally inactive. We demonstrate that the fragile 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.
Richards
R I
RI
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, Adelaide, SA, Australia.
Holman
K
K
Yu
S
S
Sutherland
G R
GR
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides