Functional interactions between nuclear receptors recognizing a common sequence element, the direct repeat motif spaced by one nucleotide (DR-1).
Direct repeat motifs composed of two hexamer half-sites spaced by a single nucleotide (DR-1) are recognized by several members of the nuclear hormone receptor superfamily. We examined, by means of gene transfection assays, the interplay between the DR-1-binding nuclear receptors commonly expressed in liver, peroxisome proliferator-activated receptor alpha (PPARalpha), hepatocyte nuclear factor-4 (HNF-4), and chicken ovalbumin upstream transcription factor I (COUP-TFI). Both PPARalpha and HNF-4 efficiently bound to the acyl-CoA oxidase gene enhancer element, but PPARalpha exhibited much stronger transactivation than HNF-4. As a result, HNF-4 suppressed the gene-activating function of PPARalpha, when they were expressed together, due to competition for a common binding site. On the other hand, HNF-4, but not PPARalpha, effectively bound to the apolipoprotein CIII gene element, and activated gene transcription. PPARalpha had no effect even when co-expressed with HNF-4. COUP-TFI bound to both elements, and suppressed the gene activation by PPARalpha and HNF-4. Thus, these nuclear receptors have individual functions in gene regulation, and exhibit complex compound effects when they co-exist.
Nishiyama
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Department of Life Science, Faculty of Science, Himeji Institute of Technology, Kamigori, Hyogo, 678-1297, Japan.
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Osada
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Osumi
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D000818:Animals; D001665:Binding Sites / Q000235:genetics; D051838:COUP Transcription Factor I; D002460:Cell Line; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000378:metabolism; D009711:Nucleotides; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D017421:Sequence Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C497591:Nr2f1 protein, rat; D009711:Nucleotides; D010750:Phosphoproteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors