Hepatocyte nuclear factor 1 binds to and transactivates the human but not the rat CYP7A1 promoter.
Cholesterol 7alpha-hydroxylase (CYP7A1), a liver-specific enzyme, catalyzes the rate-limiting step in the degradation pathway of cholesterol to bile acids, and thus plays a key role in cholesterol homeostasis. To elucidate the mechanisms that control hepatic expression of the human CYP7A1 gene, we are studying the promoter region. Initially, we observed that up to 40% of the overall transcriptional activity of the promoter in HepG2 cells was associated with DNA sequences from -65 to -1 of the human gene. Within this region, a binding site for the liver-enriched transcription factor HNF-1 (-56 to -49) has been identified. Binding of HNF-1 to this site leads to transcriptional activation of the human promoter. The corresponding segment from the rat CYP7A1 gene does not bind HNF-1; instead, it is bound by the orphan receptors ARP-1 (COUP-TFII) and LXRalpha, that are implicated in dietary regulation.
Palo Alto Medical Foundation Research Institute, Palo Alto, California, 94301, USA.
J
J
Chen
A D
AD
Cooper
B
B
Levy-Wilson
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D000071518:Liver X Receptors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid; D020218:Response Elements / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002790:Cholesterol 7-alpha-Hydroxylase; D004247:DNA; D004268:DNA-Binding Proteins; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D000071518:Liver X Receptors; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496489:Hnf1a protein, rat; C000605213:NR1H3 protein, human; C000605215:Nr1h3 protein, rat; C497588:Nr2f2 protein, rat; C095569:NR2F2 protein, human