Role of CCAAT enhancer-binding protein beta in the thyroid hormone and cAMP induction of phosphoenollolpyruvate carboxykinase gene transcription

Transcription of the gene for phosphoenolpyruvate carboxykinase (PEPCK) is stimulated by thyroid hormone (T-3) and cAMP. Two DNA elements in the PEPCK promoter are required for T-3 responsiveness including a thyroid hormone r esponse element and a binding site called P3(I) for the CCAAT enhancer-bind ing protein (C/EBP). Both the alpha and beta isoforms of C/EBP are highly e xpressed in the liver. C/EBP alpha contributes to the liver-specific expres sion and cAMP responsiveness of the PEPCK gene. In this study, we examined the ability of C/EBP beta when bound to the P3(I) site to regulate PEPCK ge ne expression. We report that C/EBP beta can stimulate basal expression and participate in the induction of PEPCK gene transcription by T-3 and cAMP. The cAMP-responsive element-binding protein and API proteins that contribut e to the induction by cAMP are not involved in the stimulation by T-3. A sm all region of the transactivation domain of C/EBP beta is sufficient for th e stimulation of basal expression and cAMP responsiveness. Our results sugg est that C/EBP alpha and C/EBP beta are functionally interchangeable when b ound to the P3(I) site of the PEPCK promoter.