Genetic control of spermiogenesis: insights from the CREM gene and implications for human infertility.
Male germ cell differentiation requires a highly cell-specific gene expression programme that is achieved by unique chromatin remodelling, transcriptional control, and the expression of testis-specific genes or isoforms. The regulatory processes governing gene expression in spermatogenesis have fundamentally unique requirements, including meiosis, ongoing cellular differentiation and a peculiar chromatin organization. The signalling cascades and the downstream effectors contributing to the programme of spermatogenesis are currently being unravelled, revealing the unique features of germ cell regulatory circuits. This paper reports on the unique role that CREM exerts as a master regulator. Targeted inactivation of the genes encoding CREM and ACT has been achieved. ACT selectively associates with KIF17b, a kinesin motor protein highly expressed in germ cells. It has been found that KIF17b directly determines the intracellular localization of ACT. Thus, the activity of a transcriptional co-activator is intimately coupled to the function of a kinesin via tight regulation of its intracellular localization. The conservation of these elements and of their regulatory functions in human spermatogenesis indicates that they are likely to provide important insights into understanding the molecular mechanisms of human infertility.
Krausz
Csilla
C
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, Florence 50139, Italy.
Sassone-Corsi
Paolo
P
D000818:Animals; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D060588:LIM Domain Proteins; D008297:Male; D051379:Mice; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology
D004268:DNA-Binding Proteins; C504656:FHL5 protein, human; C504657:Fhl5 protein, mouse; D060588:LIM Domain Proteins; D014157:Transcription Factors; C117930:activator of CREM in testis (ACT); D051786:Cyclic AMP Response Element Modulator