A CYCLIC-AMP RESPONSE ELEMENT IN THE ANGIOTENSIN-CONVERTING ENZYME GENE AND THE TRANSCRIPTION FACTOR CREM ARE REQUIRED FOR TRANSCRIPTION OFTHE MESSENGER-RNA FOR THE TESTICULAR ISOZYME

The angiotensin-converting enzyme (ACE) gene produces two mRNA species from tissue-specific promoters. The transcription start site of the m RNA for the smaller testicular isozyme (ACE(T)) is located within an i ntron of the larger transcription unit that encodes the pulmonary isoz yme (ACE(p)). We have previously demonstrated that a 298-base pair DNA fragment, 5' to the rabbit ACE(T) 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 i dentified a putative cyclic AMP response element present within this D NA fragment to be absolutely essential for transcriptional activation. Moreover, we observed that ACE(T) mRNA was not expressed in the teste s of mice homozygous for a null mutation in the transcription factor C REM. However, in the same mice, ACE(p) mRNA was abundantly expressed i n the lung. Our observations indicate that ACE(T) mRNA expression in t he testes is regulated by the putative cyclic AMP response element pre sent 5' to the transcription start site and the corresponding transcri ption factor CREM.