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Molecular basis of FIR-mediated c-myc transcriptional control.

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.

SUBMITTER: Cukier CD

PROVIDER: S-EPMC2964917 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Molecular basis of FIR-mediated c-myc transcriptional control.

Cukier Cyprian D CD Hollingworth David D Martin Stephen R SR Kelly Geoff G Díaz-Moreno Irene I Ramos Andres A

Nature structural & molecular biology 20100815 9

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 ex ...[more]

PMID: 20711187

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