Tip60 complex promotes expression of a differentiation factor to regulate germline differentiation in female Drosophila.
Tip60 complex promotes expression of a differentiation factor to regulate germline differentiation in female Drosophila.
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DOI：
10.1091/mbc.e18-06-0385
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发表时间：
2018-11-26
影响因子：
3.3
通讯作者：
Rangan P
中科院分区：
文献类型：
--
作者：
McCarthy A;Deiulio A;Martin ET;Upadhyay M;Rangan P
生殖系干细胞（GSC）自我更新和分化，以维持配子的连续生产。在雌性果蝇生殖系中，两种分化因子，大理石袋（bam）和良性生殖腺细胞瘤（bgcn），在干细胞子代中协同工作以促进卵子的产生。在GSC中，bam转录被来自小生境的信号转导抑制，并在干细胞子代中被激活。相比之下，bgcn在GSC和干细胞子细胞中都有转录，但关于bgcn如何转录调节知之甚少。在这里，我们发现，保守的蛋白Nipped-A的行为，通过达特相互作用的蛋白60 kDa（Tip 60）组蛋白乙酰转移酶复合物在生殖细胞，以促进GSC的女儿分化。我们发现，Nipped-A需要有效退出差距阶段2（G2）的细胞周期的GSC女儿和表达的分化因子，bgcn。Nipped-A的缺失导致GSC子体的积累。在Nipped-A生殖细胞耗竭的卵巢中，bgcn的强制表达挽救了这种分化缺陷。总之，我们的研究结果表明，Tip 60复合物协调细胞周期进程和bgcn的表达，以帮助推动GSC的女儿向分化计划。
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.