Systematic name M2486
Brief description Genes down-regulated in the liver tissue from 10 week old male mice with KLF10 [GeneID=7071] compared to wild-type littermates.
Full description or abstract The circadian timing system coordinates many aspects of mammalian physiology and behavior in synchrony with the external light/dark cycle. These rhythms are driven by endogenous molecular clocks present in most body cells. Many clock outputs are transcriptional regulators, suggesting that clock genes primarily control physiology through indirect pathways. Here, we show that Krüppel-like factor 10 (KLF10) displays a robust circadian expression pattern in wild-type mouse liver but not in clock-deficient Bmal1 knockout mice. Consistently, the Klf10 promoter recruited the BMAL1 core clock protein and was transactivated by the CLOCK-BMAL1 heterodimer through a conserved E-box response element. Profiling the liver transcriptome from Klf10(-/-) mice identified 158 regulated genes with significant enrichment for transcripts involved in lipid and carbohydrate metabolism. Importantly, approximately 56% of these metabolic genes are clock controlled. Male Klf10(-/-) mice displayed postprandial and fasting hyperglycemia, a phenotype accompanied by a significant time-of-day-dependent upregulation of the gluconeogenic gene Pepck and increased hepatic glucose production. Consistently, functional data showed that the proximal Pepck promoter is repressed directly by KLF10. Klf10(-/-) females were normoglycemic but displayed higher plasma triglycerides. Correspondingly, rhythmic gene expression of components of the lipogenic pathway, including Srebp1c, Fas, and Elovl6, was altered in females. Collectively, these data establish KLF10 as a required circadian transcriptional regulator that links the molecular clock to energy metabolism in the liver.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20385766   Authors: Guillaumond F,Gréchez-Cassiau A,Subramaniam M,Brangolo S,Peteri-Brünback B,Staels B,Fiévet C,Spelsberg TC,Delaunay F,Teboul M
Exact source Table 3S: Ratio < 1
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Mouse_RefSeq
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Version history 3.1: First introduced

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