Molecular Human Reproduction, Vol. 8, No. 11, 965-976,
November 2002
© 2002 European Society of Human Reproduction and Embryology
Testis and spermatogenesis |
Novel leader exons of the cyclic adenosine 3',5'-monophosphate response element modulator (CREM) gene, transcribed from promoters P3 and P4, are highly testis-specific in primates*
1 IHF Institute for Hormone and Fertility Research, University of Hamburg, D-22529 Hamburg and 2 Institute of Reproductive Medicine of the University of Münster, D-48149 Münster, Germany
Testicular expression of CREM is essential for spermatogenesis in the mouse. From a monkey testis cDNA library we isolated a CREM transcript isoform with a novel 5' exon 
2 which provides at its 3'-end an in-frame ATG to the downstream reading frame. 5'-RACE on human testis cDNA indicated that exon 2 is 
113 bp in size. Moreover, a second novel leader exon, 1, of 289 bp was identified and encodes a putative open reading frame of 26 amino acids. In-vitro translation and cellular expression of CREM-1 and CREM-2 splice variants cloned from human testis yielded not only full length proteins but also shorter repressor products resulting from downstream translation initiation. Upon co-transfection, products of CREM-2 cDNA repressed protein kinase A-induced activation of a CRE-driven reporter construct. RT–PCR analysis of primate tissues for CREM-2 transcripts showed abundant expression in the testis and very low levels or absence from all other tissues tested. CREM-1 mRNA was exclusively expressed in the testis. Promoters P3 and P4, flanking exons 1 and 2, were cloned and found to be non-responsive to protein kinase A in transfection assays. Furthermore, we show differential activation of P1, P3 and P4 during mouse postnatal testicular development, suggesting cell- and stage-specific regulatory mechanisms for these CREM promoters.
alternative promoter/CREM/isoform/primate spermatogenesis/testis
3 Present address: Covance Laboratories GmbH, D-48163 Münster, Germany
4 Present address: Institute of Anatomy, Developmental Biology, University of Essen, D-45122 Essen, Germany
5 To whom correspondence should be addressed at: Institute of Anatomy, Developmental Biology, University of Essen, Hufelandstraße 55, D-45122 Essen, Germany. E-mail: ruediger.behr{at}uni-essen.de
* This work was presented in part at the 83nd Annual Meeting of the Endocrine Society, June 2001, in Denver, CO, USA.
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