Cukier, CD;
Hollingworth, D;
Martin, SR;
Kelly, G;
Díaz-Moreno, I;
Ramos, A;
(2010)
Molecular basis of FIR-mediated c-myc transcriptional control.
Nature Structural & Molecular Biology
, 17
(9)
pp. 1058-1064.
10.1038/nsmb.1883.
Preview |
Text
Ramos_ukmss-31552.pdf Download (2MB) | Preview |
Abstract
The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.
Archive Staff Only
 |
View Item |
