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• W2006737346 abstract "Expansion of a CGG.CCG-repeat tract in the 5'-untranslated region of the FMR1 (Fragile X mental retardation 1) gene causes its aberrant transcription. This produces symptoms ranging from premature ovarian failure and Fragile X associated tremor and ataxia syndrome to FMR syndrome, depending on the size of the expansion. The promoter from normal alleles shows four protein-binding regions in vivo. We had previously shown that in mouse brain extracts two of these sites are bound by USF1/USF2 (upstream stimulatory factors 1 and 2) heterodimers and NRF-1 (nuclear respiratory factor-1). We also showed that these sites are involved in the positive regulation of FMR1 transcription in neuronally derived cells. In the present study, we show that Sp1 (specificity protein 1) and Sp3 are also strong positive regulators of FMR1 promoter activity. We also show that, like Sp1 and E-box-binding proteins such as USF1 and USF2, NRF-1 causes DNA bending, in this case producing a bend of 57 degrees towards the major groove. The combined effect of the four protein-induced bends on promoter geometry is the formation of a highly compact arch-like structure in which the 5' end of the promoter is brought in close proximity to the 3' end. We had previously shown that while point mutations in the GC-boxes decrease promoter activity, deletion of either one of them leads to an increase in promoter activity. We can reconcile these observations with the positive effect of Sp1 and Sp3 if protein-induced bending acts, at least in part, to bring together distally spaced factors important for transcription initiation." @default.
• W2006737346 created "2016-06-24" @default.
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• W2006737346 date "2005-02-22" @default.
• W2006737346 modified "2023-09-27" @default.
• W2006737346 title "The roles of Sp1, Sp3, USF1/USF2 and NRF-1 in the regulation and three-dimensional structure of the Fragile X mental retardation gene promoter" @default.
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• W2006737346 doi "https://doi.org/10.1042/bj20041124" @default.
• W2006737346 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1134794" @default.
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