CAMP-RESPONSE ELEMENT MODULATOR-TAU IS A POSITIVE REGULATOR OF TESTISANGIOTENSIN-CONVERTING ENZYME TRANSCRIPTION

Testis angiotensin-converting enzyme (ACE) is a unique form of ACE, on ly produced by male germ cells, and results from a testis-specific pro moter found within the ACE gene. We have investigated the role of cAMP -response element modulator (CREM)tau in testis ACE transcription. In gel shift experiments, testes nuclear proteins retard an oligonucleoti de containing the cAMP-response element (CRE) found at position -55 in the testis ACE promoter, anti-CREM antibody supershifts this complex. Competitive gel shift shows that recombinant CREM tau protein and tes tes nuclear proteins have a similar specificity of binding to the test is ACE CRE. Functional analysis using in vitro transcription and trans fection studies also demonstrate that CREM tau protein is a transcript ional activator of the testis ACE promoter. Western blot analysis iden tifies CREM tau protein in the protein-DNA complex formed between nucl ear proteins and the testis ACE CRE motif. This analysis also identifi ed other CREM isoforms in the gel-shifted complex, which are thought t o be CREM tau 1/2, CREM alpha/beta, and S-CREM. These data indicate th at CREM tau isoforms play an important role as a positive regulator in the tissue-specific expression of testis ACE.