Standard name SUMI_HNF4A_TARGETS
Systematic name M2306
Brief description Genes up-regulated in HepG2 cells (hepatocellular carcinoma, HCC) upon expression of HNF4A [GeneID=3172] and down-regulated upon knockdown of HNF4A [GeneID=3172] in these cells by RNAi.
Full description or abstract Cholesterol homeostasis is maintained by coordinate regulation of cholesterol synthesis and its conversion to bile acids in the liver. The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. The genes for these two proteins are closely linked and divergently transcribed from a common intergenic promoter region. Here, we identified a binding site for hepatocyte nuclear factor 4alpha (HNF4alpha) in the ABCG5/ABCG8 intergenic promoter, through which HNF4alpha strongly activated the expression of a reporter gene in both directions. The HNF4alpha-responsive element is flanked by two conserved GATA boxes that were also required for stimulation by HNF4alpha. GATA4 and GATA6 bind to the GATA boxes, coexpression of GATA4 and HNF4alpha leads to a striking synergistic activation of both the ABCG5 and the ABCG8 promoters, and binding sites for HNF4alpha and GATA were essential for maximal synergism. We also show that HNF4alpha, GATA4, and GATA6 colocalize in the nuclei of HepG2 cells and that a physical interaction between HNF4alpha and GATA4 is critical for the synergistic response. This is the first demonstration that HNF4alpha acts synergistically with GATA factors to activate gene expression in a bidirectional fashion.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17403900   Authors: Sumi K,Tanaka T,Uchida A,Magoori K,Urashima Y,Ohashi R,Ohguchi H,Okamura M,Kudo H,Daigo K,Maejima T,Kojima N,Sakakibara I,Jiang S,Hasegawa G,Kim I,Osborne TF,Naito M,Gonzalez FJ,Hamakubo T,Kodama T,Sakai J
Exact source Table 2
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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Version history 3.1: First introduced

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