title: The two PAR leucine zipper proteins, TEF and DBP, display similar circadian and tissue-specific expression, but have different target promoter preferences.
abstract: The two highly related PAR basic region leucine zipper proteins TEF and DBP accumulate according to a robust circadian rhythm in liver and kidney. In liver nuclei, the amplitude of daily oscillation has been estimated to be 50-fold and 160-fold for TEF and DBP, respectively. While DBP mRNA expression is the principal determinant of circadian DBP accumulation, the amplitude of TEF mRNA cycling is insufficient to explain circadian TEF fluctuation. Conceivably, daily variations in TEF degradation or nuclear translocation efficiency may explain the discrepancy between mRNA and protein accumulation. In vitro, TEF and DBP bind the same DNA sequences. Yet, in co-transfection experiments, these two proteins exhibit different activation potentials for two reporter genes examined. While TEF stimulates transcription from the albumin promoter more potently than DBP, only DBP is capable of activating transcription efficiently from the cholesterol 7 alpha hydroxylase (C7alphaH) promoter. However, a TEF-DBP fusion protein, carrying N-terminal TEF sequences and the DNA binding/dimerization domain of DBP, enhances expression of the C7alphaH-CAT reporter gene as strongly as wild-type DBP. Our results suggest that the promoter environment, rather than the affinity with which PAR proteins recognize their cognate DNA sequences in vitro, determines the promoter preferences of TEF and DBP.
authors.affiliation: Département de Biologie Moléculaire, Université de Genève, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Fonjallaz
authors.forename: V
authors.initials: V
authors.lastname: Ossipow
authors.forename: G
authors.initials: G
authors.lastname: Wanner
authors.forename: U
authors.initials: U
authors.lastname: Schibler
mesh_terms: D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D002940:Circadian Rhythm; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D016350:Leucine Zippers; D008113:Liver Neoplasms; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D009928:Organ Specificity; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C063898:DBP protein, human; C485975:DBP protein, rat; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C489490:TEF protein, human; D014157:Transcription Factors; C071247:Tef protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase