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J Biol Chem, Vol. 273, Issue 16, 9971-9975, April 17, 1998

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

Sean P. Kessler, Theresa M. Rowe, Julie A. Blendy^§, Robert P. Erickson^¶, and Ganes C. Sen

From the  Department of Molecular Biology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, the ^§ Department of Pharmacology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, and the ^¶ Departments of Pediatrics and Molecular and Cellular Biology, University of Arizona, College of Medicine, Tucson, Arizona 85724

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 (ACE_T) is located within an intron of the larger transcription unit that encodes the pulmonary isozyme (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 identified a putative cyclic AMP response element present within this DNA fragment to be absolutely essential for transcriptional activation. Moreover, we observed that ACE_T mRNA was not expressed in the testes of mice homozygous for a null mutation in the transcription factor CREM. However, in the same mice, ACE_P mRNA was abundantly expressed in the lung. Our observations indicate that ACE_T 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.

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