Liver-specific gene expression: A-activator-binding site, a promoter module present in vitellogenin and acute-phase genes.
The A2 vitellogenin gene of Xenopus laevis, which is expressed liver specifically, contains an A-activator-binding site (AABS) that mediates high in vitro transcriptional activity in rat liver nuclear extracts. Footprint experiments with DNase I and gel retardation assays revealed the binding of several proteins to AABS. Using binding sites of known DNA-binding proteins as competitors in the gel retardation assay, we found that the transcription factor C/EBP and/or one of its "iso-binders" as well as LFB1/HNF1 bound AABS. These interactions were confirmed by in vitro transcription experiments using various oligonucleotides as competitors. However, saturating amounts of C/EBP- and LFB1/HNF1-binding sites as competitors only partially blocked AABS-mediated transcriptional activity. This finding implies that at least a third distinct transcription factor interacts with AABS. In vitro transcription experiments revealed that AABS was present not only in the closely related Xenopus A1 vitellogenin gene but also in acute-phase genes as a liver-specific regulatory element known to confer the interleukin-6 response. Both AABS and the interleukin-6 response element are promoter modules interacting with at least three distinct transcription factors, including C/EBP and LFB1/HNF1.
Kernforschungszentrum Karlsruhe, Institut für Genetik und Toxikologie, Federal Republic of Germany.
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Kaling
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Kugler
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Ross
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Zoidl
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Ryffel
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D008099:Liver / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic; D051381:Rats; D011919:Rats, Inbred Strains; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D014819:Vitellogenins / Q000235:genetics*
D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496489:Hnf1a protein, rat; D009687:Nuclear Proteins; D009841:Oligonucleotides; D014157:Transcription Factors; D014819:Vitellogenins; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta