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Tip60 complex promotes expression of a differentiation factor to regulate germline differentiation in female Drosophila

机译:Tip60复合物可促进分化因子的表达,从而调节果蝇雌性的种系分化

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Germline stem cells (GSCs) self-renew and differentiate to sustain a continuous production of gametes. In the female Drosophila germ line, two differentiation factors, bag of marbles (bam) and benign gonial cell neoplasm (bgcn), work in concert in the stem cell daughter to promote the generation of eggs. In GSCs, bam transcription is repressed by signaling from the niche and is activated in stem cell daughters. In contrast, bgcn is transcribed in both the GSCs and stem cell daughters, but little is known about how bgcn is transcriptionally modulated. Here we find that the conserved protein Nipped-A acts through the Tat interactive protein 60-kDa (Tip60) histone acetyl transferase complex in the germ line to promote GSC daughter differentiation. We find that Nipped-A is required for efficient exit from the gap phase 2 (G2) of cell cycle of the GSC daughter and for expression of a differentiation factor, bgcn. Loss of Nipped-A results in accumulation of GSC daughters. Forced expression of bgcn in Nipped-A germline-depleted ovaries rescues this differentiation defect. Together, our results indicate that Tip60 complex coordinates cell cycle progression and expression of bgcn to help drive GSC daughters toward a differentiation program.
机译:种系干细胞(GSC)自我更新并分化,以维持配子的连续生产。在雌性果蝇种系中,两个分化因子,一袋大理石(bam)和良性角质细胞瘤(bgcn),在干细胞女儿中协同工作,促进卵的产生。在GSC中,Bam转录受到来自利基的信号传导的抑制,并在干细胞子代中被激活。相比之下,bgcn在GSC和干细胞子代中均被转录,但对bgcn如何被转录调控知之甚少。在这里,我们发现保守蛋白Nipped-A通过种系中的Tat相互作用蛋白60-kDa(Tip60)组蛋白乙酰转移酶复合物起作用,以促进GSC子代分化。我们发现Nipped-A是有效退出GSC子代细胞周期的间隙阶段2(G2)和表达分化因子bgcn所必需的。 Nipped-A的丢失导致GSC子代的积累。在Nipped-A种系缺失的卵巢中强制表达bgcn可以挽救这种分化缺陷。在一起,我们的结果表明Tip60复合体协调细胞周期进程和bgcn的表达,以帮助驱动GSC女儿走向分化程序。

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