Filipponi Doria, Hobbs Robin M, Ottolenghi Sergio, Rossi Pellegrino, Jannini Emmanuele A, Pandolfi Pier Paolo, Dolci Susanna
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Via Montpellier 1, Ed E Nord, Rome, Italy.
Mol Cell Biol. 2007 Oct;27(19):6770-81. doi: 10.1128/MCB.00479-07. Epub 2007 Jul 30.
Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion of the spermatogonial stem cell population. This is likely due to the deregulated expression of genes controlling the switch between spermatogonial self-renewal and differentiation. Here we show that Plzf directly represses the transcription of kit, a hallmark of spermatogonial differentiation. Plzf represses both endogenous kit expression and expression of a reporter gene under the control of the kit promoter region. A discrete sequence of the kit promoter, required for Plzf-mediated kit transcriptional repression, is bound by Plzf both in vivo and in vitro. A 3-bp mutation in this Plzf binding site abolishes the responsiveness of the kit promoter to Plzf repression. A significant increase in kit expression is also found in the undifferentiated spermatogonia isolated from Plzf(-/-) mice. Thus, we suggest that one mechanism by which Plzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression.
缺乏DNA序列特异性转录抑制因子Plzf表达的雄性小鼠，由于精原干细胞群体的耗竭而出现渐进性生殖细胞减少。这可能是由于控制精原细胞自我更新和分化之间转换的基因表达失调所致。在这里，我们表明Plzf直接抑制kit的转录，kit是精原细胞分化的一个标志。Plzf既抑制内源性kit表达，也抑制在kit启动子区域控制下的报告基因的表达。Plzf介导的kit转录抑制所需的kit启动子的一个离散序列，在体内和体外均被Plzf结合。该Plzf结合位点的一个3碱基突变消除了kit启动子对Plzf抑制的反应性。在从Plzf(-/-)小鼠分离的未分化精原细胞中也发现kit表达显著增加。因此，我们认为Plzf维持精原干细胞池的一种机制是通过直接抑制kit表达。
