Abstract
We have examined the effects of an adenosine 3',5'-cyclic monophosphate (cAMP) analog on human aldolase C gene expression in the rat pheochromocytoma cell line PC12. Incubation for 4 h with 500 microM 8-Br-cAMP increased aldolase C mRNA expression 2.5-fold and the expression was still above basal level 24 h later. Using transient transfection experiments we demonstrate that the distal element D in the promoter region of the human aldolase C gene, which binds a transcriptional activator (NGFI-B), is involved in this regulation. NGFI-B mRNA and protein expression were promptly (15 min) increased after 8-Br-cAMP treatment and precedes aldolase C mRNA increase (30 min). After 4 h of 8-Br-cAMP treatment, the binding of NGFI-B protein to the distal element D in the distal promoter region was increased twofold and this correlates with the increased expression of the clone that contains distal element D. These results indicate that the distal element D in the promoter region of the human aldolase C gene is the target of a cAMP-dependent regulation pathway.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
8-Bromo Cyclic Adenosine Monophosphate / pharmacology
-
Animals
-
Chloramphenicol O-Acetyltransferase / drug effects
-
Chloramphenicol O-Acetyltransferase / genetics
-
Chloramphenicol O-Acetyltransferase / metabolism
-
Cyclic AMP / pharmacology*
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Fructose-Bisphosphate Aldolase / genetics*
-
Gene Expression / genetics
-
Gene Expression Regulation, Enzymologic / drug effects
-
Humans
-
Nuclear Receptor Subfamily 4, Group A, Member 1
-
PC12 Cells
-
Promoter Regions, Genetic / genetics
-
Protein Binding / drug effects
-
RNA, Messenger / drug effects
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
Rats
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Steroid
-
Recombinant Fusion Proteins / drug effects
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Response Elements / genetics
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
Up-Regulation / drug effects
Substances
-
DNA-Binding Proteins
-
NR4A1 protein, human
-
Nr4a1 protein, rat
-
Nuclear Receptor Subfamily 4, Group A, Member 1
-
RNA, Messenger
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Steroid
-
Recombinant Fusion Proteins
-
Transcription Factors
-
8-Bromo Cyclic Adenosine Monophosphate
-
Cyclic AMP
-
Chloramphenicol O-Acetyltransferase
-
Fructose-Bisphosphate Aldolase