THE 2 PAR LEUCINE-ZIPPER PROTEINS, TEF AND DBP, DISPLAY SIMILAR CIRCADIAN AND TISSUE-SPECIFIC EXPRESSION, BUT HAVE DIFFERENT TARGET PROMOTER PREFERENCES

The two highly related PAR basic region leucine zipper proteins TEF an d DBP accumulate according to a robust circadian rhythm in liver and k idney, In liver nuclei, the amplitude of daily oscillation has been es timated to be 50-fold and 160-fold for TEF and DBP respectively, While DBP mRNA expression is the principal determinant of circadian DBP acc umulation, the amplitude of TEF mRNA cycling is insufficient to explai n circadian TEF fluctuation. Conceivably, daily variations in TEF degr adation or nuclear translocation efficiency may explain the discrepanc y between mRNA and protein accumulation, in vitro, TEF and DBP bind th e same DNA sequences, Yet, in co-transfection experiments, these two p roteins exhibit different activation potentials for two reporter genes examined, While TEF stimulates transcription from the albumin promote r more potently than DBP only DBP is capable of activating transcripti on efficiently from the cholesterol 7 alpha hydroxylase (C7 alpha H) p romoter. However, a TEF-DBP fusion protein, carrying N-terminal TEF se quences and the DNA binding/dimerization domain of DBP, enhances expre ssion of the C7 alpha H-CAT reporter gene as strongly as wild-type DBP Our results suggest that the promoter environment, rather than the af finity with which PAR proteins recognize their cognate DNA sequences i n vitro, determines the promoter preferences of TEF and DBP.