THE PROMOTER REGULATORY REGIONS OF THE GENES FOR THE CYTOSOLIC FORM OF PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP) FROM THE CHICKEN AND THE RATHAVE DIFFERENT SPECIES-SPECIFIC ROLES IN GLUCONEOGENESIS

Hepatic expression of the gene for phosphoenolpyruvate carboxykinase ( GTP) (PEPCK-C) (EC 4.1.1.32) in birds occurs prior to birth and decrea ses to negligible levels before hatching, whereas in mammals the gene for PEPCK-C in the liver is expressed at birth and is active throughou t the life of the animal, The administration of cyclic AMP to adult ch ickens results in the induction of transcription of the gene for PEPCK -C and the transient accumulation of PEPCK-C mRNA in the liver. DNase I footprint analysis of 330 bp of the avian PEPCK-C promoter immediate ly 5' of the start-site of transcription indicated the presence of sev eral protein binding domains, purified CAAT/enhancer binding protein a lpha, cAMP regulatory element binding protein and nuclear factor-1 bou nd to these regions of the promoter. Sequences corresponding to an hep atic nuclear factor-1 binding domain and to the insulin response seque nce, previously identified in the rat PEPCK-C promoter, were also foun d in the chicken PEPCK-C promoter, Co-transfection of an expression ve ctor for CAAT/enhancer binding protein alpha or CAAT/enhancer binding protein beta markedly stimulated transcription from both the chicken a nd rat PEPCK-C promoters in human hepatoma cells, Sequences involved i n the regulation of gene transcription by cyclic AMP and insulin were found to reside between -210 and +1 of the avian PEPCK-C promoter. In general, transcription from the avian promoter was more sensitive to i nhibition by insulin than was noted for the rat PEPCK-C promoter, whic h may explain in part the lack of expression of the gene for PEPCK-C i n the livers of adult birds.