Identification of a cAMP response element within the glucose-6-phosphatasehydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone a nd dibutyryl cAMP in H4IIE hepatoma cells, A cis-active element located bet ween nucleotides -161 and - 152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expre ssion and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus seque nce for a cAMP response element. An antibody against the cAMP response elem ent-binding protein caused a supershift in gel-electrophoretic-mobility-shi ft assays using an oligonucleotide probe representing the glucose 6-phospha tase gene promoter from nucleotides -161 to -152. These results strongly in dicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the re gulation of transcription of the glucose 6-phosphatase gene by both cAMP an d glucocorticoids.