INDUCTION OF CREM ACTIVATOR PROTEINS IN SPERMATIDS - DOWN-STREAM TARGETS AND IMPLICATIONS FOR HAPLOID GERM-CELL DIFFERENTIATION

The cAMP-responsive element modulator (CREM) gene encodes a family of transcriptional regulators that bind to promoter sequences activated b y increased intracellular cAMP levels. Both activators and repressors are generated by alternative splicing and alternative translational in itiation. During the development of male germ cells, there is a switch in the transcripts generated by CREM. Specifically, from the prophase of meiosis, there is an increase in the CREM tau activator transcript . Here we present results showing that expression of the CREM activato r protein is restricted to postmeiotic germ cells. We show that CREM t au is efficiently phosphorylated at a serine residue at position 117 b y the protein kinase-A endogenous to germ cells, indicating that it co nstitutes a natural target of the adenylyl cyclase pathway during sper matogenesis. Phosphorylation of serine-117 turns CREM tau into a power ful activator. The rise in CREM tau protein coincides with the transcr iptional activation of several genes. We show that CREM tau efficientl y binds to CREs present in the promoters of these genes, suggesting th at they could constitute down-stream targets of CREM. We have analyzed in more detail the regulation of one of these genes, the male germ ce ll-specific RT7. The RT7 promoter is cAMP inducible and activated by C REM tau in transfection assays. The RT7 promoter is efficently transcr ibed in vitro with nuclear extracts from seminiferous tubules. CREM-sp ecific antibodies block RT7 in vitro transcription, implicating a role for CREM tau in a cascade of transcriptional events during spermatoge nesis.