Gene Set: BOCHKIS_FOXA2_TARGETS

Standard name BOCHKIS_FOXA2_TARGETS
Systematic name M1806
Brief description Direct targets of FOXA2 [GeneID=3170] in liver, according to a ChIP-chip analysis.
Full description or abstract Production of bile by the liver is crucial for the absorption of lipophilic nutrients. Dysregulation of bile acid homeostasis can lead to cholestatic liver disease and endoplasmic reticulum (ER) stress. We show by global location analysis ('ChIP-on-chip') and cell type-specific gene ablation that the winged helix transcription factor Foxa2 is required for normal bile acid homeostasis. As suggested by the location analysis, deletion of Foxa2 in hepatocytes in mice using the Cre-lox system leads to decreased transcription of genes encoding bile acid transporters on both the basolateral and canalicular membranes, resulting in intrahepatic cholestasis. Foxa2-deficient mice are strikingly sensitive to a diet containing cholic acid, which results in toxic accumulation of hepatic bile salts, ER stress and liver injury. In addition, we show that expression of FOXA2 is markedly decreased in liver samples from individuals with different cholestatic syndromes, suggesting that reduced FOXA2 abundance could exacerbate the injury.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18660816   Authors: Bochkis IM,Rubins NE,White P,Furth EE,Friedman JR,Kaestner KH
Exact source Table 1S
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Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform SEQ_ACCESSION
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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