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Molecular basis of FIR-mediated c-myc transcriptional control

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. Green open access

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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.

Type: Article
Title: Molecular basis of FIR-mediated c-myc transcriptional control
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nsmb.1883
Publisher version: http://doi.org/10.1038/nsmb.1883
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Gene regulation, Oncogenes, Transcription
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1403851
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