Molecular basis of FIR-mediated c-myc transcriptional control

Cukier, Cyprian D; Hollingworth, David; Martin, Stephen R; Kelly, Geoff; Díaz-Moreno, Irene; Ramos, Andres
September 2010
Nature Structural & Molecular Biology;Sep2010, Vol. 17 Issue 9, p1058
Academic Journal
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.


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