E-GEOD-44609 - Usf1, a Suppressor of the Circadian Clock Mutant, Reveals the Nature of the DNA-binding of the CLOCK:BMAL1 complex in mice

Released on 21 April 2013, last updated on 29 April 2013
Mus musculus
Samples (13)
Protocols (3)
Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock. Here, we demonstrate that the ClockΔ19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. We map a suppressor of the ClockΔ19 mutation to a ∼900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene. A SNP in the promoter of Usf1 causes elevation of its transcript and protein in strains that suppress the Clock mutant phenotype. USF1 competes with the CLOCK:BMAL1 complex for binding to E-box sites in target genes. Saturation binding experiments demonstrate reduced affinity of the CLOCKΔ19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis. We propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals. DOI:http://dx.doi.org/10.7554/eLife.00426.001. Examination of 3 transcriptional regulators in mouse liver at ZT8
Experiment type
Joseph S Takahashi <joseph.takahashi@utsouthwestern.edu>, Kazuhiro Shimomura, Nobuya Koike, Tae-Kyung Kim, Vivek Kumar
Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice. Shimomura K, Kumar V, Koike N, Kim TK, Chong J, Buhr ED, Whiteley AR, Low SS, Omura C, Fenner D, Owens JR, Richards M, Yoo SH, Hong HK, Vitaterna MH, Bass J, Pletcher MT, Wiltshire T, Hogenesch J, Lowrey PL, Takahashi JS. , PMID:23580255
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