Transcriptional cascades during spermatogenesis: pivotal role of CREM and ACT.
The gene CREM plays key physiological and developmental roles within the hypothalamic--pituitary--gonadal axis. We have previously shown that CREM is highly expressed in male postmeiotic cells. Spermiogenesis is a complex process by which postmeiotic male germ cells differentiate into mature spermatozoa. CREM regulates the expression of a number of post-meiotic genes involved in the process of spermiogenesis. Using homologous recombination we have generated CREM-mutant mice that display a complete block at the first step of spermiogenesis. The molecular mechanism by which CREM elicits its regulatory function involves ACT (Activator of CREM in Testis), a testis-specific coactivator constituted by a repeat of four and half LIM domains. ACT is coordinately expressed with CREM, associates with it and confers a powerful transcriptional activation function. It is able to bypass the classical requirement of CREM phosphorylation and recruiting of CBP.
Fimia
G M
GM
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS-INSERM-Université Louis Pasteur, B.P. 163, Illkirch, 67404 Strasbourg, France.
Morlon
A
A
Macho
B
B
De Cesare
D
D
Sassone-Corsi
P
P
D000818:Animals; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D008297:Male; D012097:Repressor Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology*; D013094:Spermatozoa / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics*
D004268:DNA-Binding Proteins; C504656:FHL5 protein, human; C504657:Fhl5 protein, mouse; D060588:LIM Domain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C117930:activator of CREM in testis (ACT); D051786:Cyclic AMP Response Element Modulator