Human aldolase C gene expression is regulated by adenosine 3',5'-cyclic monophosphate (cAMP) in PC12 cells.
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.
Buono
Pasqualina
P
Facoltà di Scienze Motorie, Università degli Studi di Napoli Parthenope, via Acton 38, 80125 Naples, Italy.
Cassano
Silvana
S
Alfieri
Andreina
A
Mancini
Annamaria
A
Salvatore
Francesco
F
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics*; D015870:Gene Expression / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016716:PC12 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase; D005634:Fructose-Bisphosphate Aldolase