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.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
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 Jdoi
10.1128/MCB.01894-06subject
Has Abstractpub_date
2007-06-01 00:00:00pages
4248-60issue
12eissn
0270-7306issn
1098-5549pii
MCB.01894-06journal_volume
27pub_type
杂志文章abstract::Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the functio...
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