Repression of kit expression by Plzf in germ cells
Repression of kit expression by Plzf in germ cells
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DOI：
10.1128/mcb.00479-07
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Dolci, Susanna
中科院分区：
文献类型：
--
作者：
Filipponi, Doria;Hobbs, Robin M.;Dolci, Susanna
缺乏DNA序列特异性转录抑制因子PLZF的雄性小鼠，由于精原干细胞种群的耗尽，表现出进行性生殖细胞枯竭。这可能是由于控制精原细胞自我更新和分化之间的开关的基因表达失控。在这里，我们发现PLZF直接抑制KIT的转录，KIT是精原细胞分化的标志。PLZF在KIT启动子区域的控制下抑制内源性KIT的表达和报告基因的表达。PLZF介导的KIT转录抑制所需的KIT启动子的离散序列在体内和体外都与PLZF结合。这个P`lzf结合位点上的3个碱基突变取消了KIT启动子对PLZF抑制的反应性。从PLZF(-/-)小鼠分离的未分化精原细胞中KIT的表达也显著增加。因此，我们认为P`lzf维持精原干细胞库的一个机制是通过直接抑制KIT的表达。
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 P`lzf 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 P`lzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression.