A cyclic AMP response element in the angiotensin-converting enzyme gene and the transcription factor CREM are required for transcription of the mRNA for the testicular isozyme.
The angiotensin-converting enzyme (ACE) gene produces two mRNA species from tissue-specific promoters. The transcription start site of the mRNA for the smaller testicular isozyme (ACET) is located within an intron of the larger transcription unit that encodes the pulmonary isozyme (ACEP).We have previously demonstrated that a 298-base pair DNA fragment, 5' to the rabbit ACET mRNA transcription initiation site, can activate the testicular expression of a transgenic reporter gene. In the current study, using the same transgenic reporter system, we identified a putative cyclic AMP response element present within this DNA fragment to be absolutely essential for transcriptional activation. Moreover, we observed that ACET mRNA was not expressed in the testes of mice homozygous for a null mutation in the transcription factor CREM. However, in the same mice, ACEP mRNA was abundantly expressed in the lung. Our observations indicate that ACET mRNA expression in the testes is regulated by the putative cyclic AMP response element present 5' to the transcription start site and the corresponding transcription factor CREM.
Kessler
S P
SP
Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Rowe
T M
TM
Blendy
J A
JA
Erickson
R P
RP
Sen
G C
GC
D000818:Animals; D001921:Brain / Q000201:enzymology; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D013737:Testis / Q000201:enzymology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D015500:Chloramphenicol O-Acetyltransferase; D007703:Peptidyl-Dipeptidase A