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Title

Molecular basis of FIR-mediated c-myc transcriptional control

AuthorsCukier, Cyprian D.; Hollingworth, David; Martin, Stephen; Kelly, Geoff; Díaz-Moreno, Irene ; Ramos, Andrés
KeywordsFar Upstream element
FUSE
FIR
C-myc
FBP
Issue Date15-Aug-2010
PublisherNature Publishing Group
CitationNature Structural and Molecular Biology 17(9): 1058-1064 (2010)
AbstractThe 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.
Description19 páginas, 7 figuras, 1 tabla
Publisher version (URL)http://dx.doi.org/10.1038/nsmb.1883
URIhttp://hdl.handle.net/10261/33710
DOI10.1038/nsmb.1883
ISSN1545-9993
Appears in Collections:(IBVF) Artículos
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