Mapping Data

Experiment

• Experiment
  TEXT-QTL
• Chromosome
  1
• Reference
  J:198519 Shimomura K, et al., Usf1, a suppressor of the circadian Clock mutant, reveals the nature of the DNA-binding of the CLOCK:BMAL1 complex in mice. Elife. 2013;2:e00426
• ID
  MGI:6756393

Genes

Gene	Assay Type
Soc1	visible phenotype

Notes

• Experiment
  To adapt to daily environmental cycles, most organisms have evolved endogenous clocks composed of cell-autonomous, self-sustained oscillators that drive 24-hr rhythms in biochemistry, physiology and behavior. Genetic and molecular approaches have been critical for elucidating the mechanism of the mammalian circadian clock.
  
  Here, the authors demonstrate that the Clock-delta-19 mutant behavioral phenotype is significantly modified by mouse strain genetic background. They map a suppressor of the Clock-delta-19 mutation to a ~900 kb interval on mouse chromosome 1 and identify the transcription factor, Usf1, as the responsible gene.
  
  To assess whether suppressor alleles segregate in the BALB/cJ x C57BL/6J hybrids, the authors analyzed the circadian locomotor activity rhythm of Clock^delta-19/+ mice from five different populations between the BALB/cJ and C57BL/6J strains. Analysis of period in these crosses suggests that the BALB/cJ allele acts semidominantly to suppress the Clock-delta-19 mutation.
  
  To map the Clock suppressor loci, the authors used the (BALB/cJ x C57BL/6J)F2 generation. They performed QTL analysis on 222 (BALB/cJ x C57BL/6J)F2 Clock^delta-19/+ mice with 87 simple sequence length polymorphism markers (SSLP) and detected a significant association between Clock-delta-19 phenotype suppression and a locus on mouse chromosome 1 (genome coordinates relative to GRCm38/mm10):
  
  Soc1 (suppressor of Clock 1) maps to Chr 1: 165.1 - 190.45 Mb.
  
  The authors identify Usf1 as the primary candidate gene underlying Soc1. 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 CLOCK-delta-19:BMAL1 complex for E-box sites, thereby permitting increased USF1 occupancy on a genome-wide basis.
  
  The authors propose that USF1 is an important modulator of molecular and behavioral circadian rhythms in mammals.