THE PEM HOMEOBOX GENE - ANDROGEN-DEPENDENT AND ANDROGEN-INDEPENDENT PROMOTERS AND TISSUE-SPECIFIC ALTERNATIVE RNA SPLICING

The Pem gene encodes an atypical homeodomain protein, distantly relate d to Prd/Pax family members, that we demonstrate is regulated in a com plex transcriptional and post-transcriptional manner. We show that the rat Pem genomic structure includes three 5'-untranslated (5'-UT) exon s and four coding exons, three of which encode the homeodomain, Severa l alternatively spliced transcripts were identified, including one tha t skips an internal coding exon, enabling this mRNA to express a novel form of the Pem protein, Other alternatively spliced mRNAs were chara cterized that possess different 5'-UT regions, including a muscle spec ific transcript, The different 5'-UT termini present in Pem transcript s conferred different levels of translatability in vitro. Two promoter s containing multiple transcription initiation sites were identified: a distal promoter (P-d) in the first 5'-UT exon and a proximal promote r (P-p) located in the ''intron'' upstream of the first coding exon, T he P-d was active in placenta, ovary, tumor cell Lines, and to a lesse r extent in skeletal muscle, In contrast, transcripts from the P-p wer e only detectable in testis and epididymis and were only expressed in epididymis in the presence of testosterone, To our knowledge no transc ription factors have previously been identified that exhibit androgen- dependent expression in the epididymis.