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The Journal of Nutrition Vol. 127 No. 2 February 1997, pp. 276-285
Copyright ©1997 by the American Society for Nutritional Sciences

The Promoter Regulatory Regions of the Genes for the Cytosolic Form of Phosphoenolpyruvate Carboxykinase (GTP) from the Chicken and the Rat Have Different Species-Specific Roles in Gluconeogenesis

Manuscript received 20 November 1995. Initial reviews completed 14 December 1995. Revision accepted 28 October 1996.

Summer P. Savon, Parvin Hakimi, Deborah R. Crawford, Dwight J. Klemm, Austin L. Gurney, and Richard W. Hanson

Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4935

Hepatic expression of the gene for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 4.1.1.32) in birds occurs prior to birth and decreases to negligible levels before hatching, whereas in mammals the gene for PEPCK-C in the liver is expressed at birth and is active throughout the life of the animal. The administration of cyclic AMP to adult chickens 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 immediately 5' of the start-site of transcription indicated the presence of several protein binding domains, purified CAAT/enhancer binding protein alpha , cAMP regulatory element binding protein and nuclear factor-1 bound to these regions of the promoter. Sequences corresponding to an hepatic nuclear factor-1 binding domain and to the insulin response sequence, previously identified in the rat PEPCK-C promoter, were also found in the chicken PEPCK-C promoter. Co-transfection of an expression vector for CAAT/enhancer binding protein alpha  or CAAT/enhancer binding protein beta  markedly stimulated transcription from both the chicken and rat PEPCK-C promoters in human hepatoma cells. Sequences involved in 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 inhibition by insulin than was noted for the rat PEPCK-C promoter, which may explain in part the lack of expression of the gene for PEPCK-C in the livers of adult birds.

Key words: phosphoenolpyruvate carboxykinase, birds, transcription factors, insulin, cAMP.




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C. Croniger, P. Leahy, L. Reshef, and R. W. Hanson
C/EBP and the Control of Phosphoenolpyruvate Carboxykinase Gene Transcription in the Liver
J. Biol. Chem., November 27, 1998; 273(48): 31629 - 31632.
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Copyright © 1997 by American Society for Nutrition