MAMMALIAN spermatogenesis consists of a series of complex developmental processes controlled by the pituitary–hypothalamic axis1. This flow of biochemical information is directly regulated by the adenylate cyclase signal transaction pathway2. We have previously described the CREM (cyclic AMP-responsive element modulator) gene which generates, by cell-specific splicing, alternative antagonists of the cAMP transcriptional response3. Here we report the expression of a novel CREM isoform (CREMτ) in adult testis. CREMτ differs from the previously characterized CREM antagonists by the coordinate insertion of two glutamine-rich domains that confer transcriptional activation function. During spermatogenesis there was an abrupt switch in CREM expression. In premeiotic germ cells CREM is expressed at low amounts in the antagonist form. Subsequently, from the pachytene spermatocyte stage onwards, a splicing event generates exclusively the CREMτ activator, which accumulates in extremely high amounts. This splicing-dependent reversal in CREM function represents an important example of developmental modulation in gene expression.
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Foulkes, N., Mellström, B., Benusiglio, E. et al. Developmental switch of CREM function during spermatogenesis: from antagonist to activator. Nature 355, 80–84 (1992). https://doi.org/10.1038/355080a0
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