Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4).
Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) and hepatocyte nuclear factor-4 (HNF-4) are orphan members of the steroid/thyroid receptor superfamily and exhibit ubiquitous and liver-enriched tissue distribution, respectively. The gene for rat ornithine transcarbamylase (OTC), an ornithine cycle enzyme, is mainly expressed in the liver and is under the control of the promoter and the 11-kilobase upstream enhancer, both of which are liver-selective. Two sites of the promoter region and two sites of the enhancer region of the OTC gene, as well as the ovalbumin promoter site, were recognized by both HNF-4 and COUP-TF, showing that these two factors have closely related binding specificities. Since HNF-4 activated expression from the OTC promoter in cotransfection analysis, this factor appears to participate in liver-selective activation of the OTC gene. On the other hand, COUP-TF repressed the expression from the OTC promoter, whereas it activated expression from several other promoters. Therefore, COUP-TF plays a dual regulatory role depending on the promoter context. Repression of a tissue-specific promoter by a ubiquitous transactivator and derepression by a related tissue-enriched transactivator is potentially an important mechanism for tissue-specific activation of a gene.
Department of Molecular Genetics, Kumamoto University School of Medicine, Japan.
A
A
Kimura
A
A
Nishiyori
T
T
Murakami
T
T
Tsukamoto
S
S
Hata
T
T
Osumi
R
R
Okamura
M
M
Mori
M
M
Takiguchi
D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001921:Brain / Q000201:enzymology; D051838:COUP Transcription Factor I; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015971:Gene Expression Regulation, Enzymologic; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D010047:Ovalbumin / Q000235:genetics*; D010750:Phosphoproteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000201:enzymology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; C497589:NR2F1 protein, human; C497591:Nr2f1 protein, rat; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D010047:Ovalbumin; D004247:DNA; D009954:Ornithine Carbamoyltransferase