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Submitted on July 17, 2003
Accepted on September 18, 2003
1 Institut de Génétique et de Biologie Moléculaire et Cellulaire; 1, rue Laurent Fries, 67404 Illkirch, Strasbourg, France; Department of Anatomy, University of Turku, 20520 Turku, Finland
* To whom correspondence should be addressed. E-mail: paolosc{at}igbmc.u-strasbg.fr.
Regulation of gene expression in haploid male germ cells follows a number of specific rules which differ from somatic cells. In this physiological context, transcriptional control mediated by the activator CREM represents an established paradigm. In somatic cells activation by CREM requires its phosphorylation at a unique regulatory site (Ser117) and subsequent interaction with the ubiquitous coactivator CBP. In testis, CREM transcriptional activity is controlled through interaction with a tissue-specific partner, ACT, which confers a powerful, phosphorylation-independent activation capacity. In addition to specialized transcription factors and coactivators, a variety of general factors of the basal transcriptional machinery, and their distinct tissue-specific isoforms, are highly expressed in testis, supporting the general notion that testis-specific gene expression requires specialized mechanisms. Here, we describe that CREM interacts with TFIIA, a general transcription factor that stimulates RNA polymerase II-directed transcription. This association was identified by a two-hybrid screen, using a testis-derived cDNA library, and confirmed by co-immunoprecipitation. The interaction is restricted to the activator isoforms of CREM and does not require Ser117. Importantly, CREM does not interact with TFIIA
-ALF, a testis-specific TFIIA homolog. CREM and TFIIA are expressed in a spatially and temporally coordinated fashion during the differentiation program of germ cells. The two proteins also colocalize intracellularly in spermatocyte and spermatid cells. These findings contribute to the understanding of the highly specialized rules of transcriptional regulation in haploid germ cells.
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