Gene Set: IM_SREBF1A_TARGETS

Standard name IM_SREBF1A_TARGETS
Systematic name M2433
Brief description Genes differentially expressed in liver tissue upon knockout of the 1a isoform of SREBF1 [GeneID=6720].
Full description or abstract We generated a line of mice in which sterol regulatory element binding protein 1a (SREBP-1a) was specifically inactivated by insertional mutagenesis. Homozygous mutant mice were completely viable despite expressing SREBP-1a mRNA below 5% of normal, and there were minimal effects on expression of either SREBP-1c or -2. Microarray expression studies in liver, where SREBP-1a mRNA is 1/10 the level of the highly similar SREBP-1c, demonstrated that only a few genes were affected. The only downregulated genes directly linked to lipid metabolism were Srebf1 (which encodes SREBP-1) and Acacb (which encodes acetyl coenzyme A [acetyl-CoA] carboxylase 2 [ACC2], a critical regulator of fatty acyl-CoA partitioning between cytosol and mitochondria). ACC2 regulation is particularly important during food restriction. Similar to Acacb knockout mice, SREBP-1a-deficient mice have lower hepatic triglycerides and higher serum ketones during fasting than wild-type mice. SREBP-1a and -1c have identical DNA binding and dimerization domains; thus, the failure of the more abundant SREBP-1c to substitute for activating hepatic ACC2 must relate to more efficient recruitment of transcriptional coactivators to the more potent SREBP-1a activation domain. Our chromatin immunoprecipitation results support this hypothesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19564420   Authors: Im SS,Hammond LE,Yousef L,Nugas-Selby C,Shin DJ,Seo YK,Fong LG,Young SG,Osborne TF
Exact source Table 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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