Alternative titles; symbols
HGNC Approved Gene Symbol: CGGBP1
Cytogenetic location: 3p11.1 Genomic coordinates (GRCh38) : 3:88,051,950-88,149,870 (from NCBI)
CGGBP1 influences expression of the FMR1 gene (309550), which is associated with the fragile X syndrome (300624), by specifically interacting with the 5-prime (CGG)n-3-prime repeat in its 5-prime UTR.
Autonomous expansions of trinucleotide repeats with the general structure (CGG)n are associated with several human genetic disorders. Expansion of the (CGG)n repeat in the 5-prime UTR of FMR1 is accompanied by extensive methylation of the CG dinucleotides in the repeat and is associated with transcriptional silencing of the FMR1 gene. Deissler et al. (1996) identified a 20-kD HeLa cell nuclear protein, p20-CGGBP (CGG-binding protein), that specifically bound the double-stranded CGG repeat. p20-CGGBP binding was severely inhibited by complete or partial methylation of the binding motif. By searching an EST database with the partial protein sequence of p20-CGGBP, Deissler et al. (1997) identified a cDNA containing the entire p20-CGGBP coding region. The predicted 166-amino acid protein contains a putative nuclear localization signal. Northern blot analysis revealed that p20-CGGBP is expressed as a 1.2-kb transcript in HeLa cells. Dot blot hybridization indicated that this mRNA is expressed in a number of human tissues. Using Southern blots, Deissler et al. (1997) found that the p20-CGGBP gene is conserved among mammals.
Naumann et al. (2004) identified an exon 3 splice variant of CGGBP1 as well as several alternate polyadenylation signals. Northern blot analysis detected transcripts of 4.5- and 1.2-kb expressed in varying ratios in all adult and fetal tissues examined. Highest expression was in adult skeletal muscle, thymus, and pancreas. Mouse Cggbp1 was expressed in embryonic stem cells and throughout mouse embryonic development.
Naumann et al. (2004) determined that the promoter region of CGGBP1 is unmethylated in human cells, and in vitro methylation inactivated the promoter in a reporter assay. They found that CGGBP1 bound to 5-prime-(CGG)n-3-prime repeats in vitro with n equal to or greater than 5. It also bound interrupted repeats.
Naumann et al. (2004) determined that the CGGBP gene contains 4 exons, with the entire open reading frame located within exon 4. The promoter region contains CAAT boxes and several Sp1 (189906)-binding sites.
By analysis of a somatic cell hybrid panel, Deissler et al. (1997) mapped the p20-CGGBP protein to human chromosome 3. Using FISH, Naumann et al. (2004) mapped the CGGBP gene near the centromere on chromosome 3p.
Deissler, H., Behn-Krappa, A., Doerfler, W. Purification of nuclear proteins from human HeLa cells that bind specifically to the unstable tandem repeat (CGG)n in the human FMR1 gene. J. Biol. Chem. 271: 4327-4334, 1996. [PubMed: 8626781] [Full Text: https://doi.org/10.1074/jbc.271.8.4327]
Deissler, H., Wilm, M., Genc, B., Schmitz, B., Ternes, T., Naumann, F., Mann, M., Doerfler, W. Rapid protein sequencing by tandem mass spectrometry and cDNA cloning of p20-CGGBP: a novel protein that binds to the unstable triplet repeat 5-prime-d(CGG)n-3-prime in the human FMR1 gene. J. Biol. Chem. 272: 16761-16768, 1997. [PubMed: 9201980] [Full Text: https://doi.org/10.1074/jbc.272.27.16761]
Naumann, F., Remus, R., Schmitz, B., Doerfler, W. Gene structure and expression of the 5-prime-(CGG)n-3-prime-binding protein (CGGBP1). Genomics 83: 106-118, 2004. [PubMed: 14667814] [Full Text: https://doi.org/10.1016/s0888-7543(03)00212-x]