dBre1/dSet1-dependent pathway for histone H3K4 trimethylation has essential roles in controlling germline stem cell maintenance and germ cell differentiation in the Drosophila ovary
dBre1/dSet1-dependent pathway for histone H3K4 trimethylation has essential roles in controlling germline stem cell maintenance and germ cell differentiation in the Drosophila ovary
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dBre1/dSet1 依赖的组蛋白 H3K4 三甲基化途径在控制果蝇卵巢生殖干细胞维持和生殖细胞分化中发挥重要作用
DOI：
10.1016/j.ydbio.2013.04.015
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发表时间：
2013-07-15
影响因子：
2.7
通讯作者：
Li, Mingfa
中科院分区：
文献类型：
--
作者：
Xuan, Tao;Xin, Tianchi;Li, Mingfa
果蝇卵巢生殖干细胞（GSC）不断自我更新和分化，确保女性一生的生育能力。 GSC自我更新和分化之间的平衡受到干细胞生态位、干细胞本身和全身因素的精细调节。越来越多的证据表明，GSC 调控还涉及表观遗传机制，包括染色质重塑和组蛋白修饰。在这里，我们发现 dBre1（一种 E3 泛素连接酶）通过不同的机制发挥控制 GSC 自我更新和生殖细胞分化的作用。种系或体细胞生态位细胞谱系中 dBrel 功能的去除或敲低会导致果蝇卵巢中 GSC 逐渐丧失和 H3K4 三甲基化破坏。进一步的研究表明，GSC 维持缺陷可归因于干细胞生态位发出的 BMP 信号受损以及 GSC 与其生态位的粘附受损。另一方面，护卫细胞中 dBre1-RNAi 的表达会导致 H3K4 三甲基化的丧失以及含有光谱体的单个生殖细胞在生殖细胞中的积累。降低 dpp 或 dally 水平可抑制生殖细胞分化缺陷，表明 dBrel 限制用于分化控制的 BMP 信号传导活性。引人注目的是，在 dBrel 突变体卵巢中观察到的所有表型都可以通过基于 RNAi 的 dSet1（一种果蝇 H3K4 三甲基化酶）表达减少来模拟。此外，遗传学研究表明 dBrel 与 dSet1 相互作用，可控制 GSC 维持和生殖细胞分化。综上所述，我们确定了参与果蝇卵巢细胞命运调节的 H3K4 甲基化的 dBre1/dSet1 依赖性途径。 (C) 2013 Elsevier Inc. 保留所有权利。
The Drosophila ovarian germline stem cells (GSCs) constantly experience self-renewal and differentiation, ensuring the female fertility throughout life. The balance between GSC self-renewal and differentiation is exquisitely regulated by the stem cell niche, the stem cells themselves and systemic factors. Increasing evidence has shown that the GSC regulation also involves epigenetic mechanisms including chromatin remodeling and histone modification. Here, we find that dBre1, an E3 ubiquitin ligase, functions in controlling GSC self-renewal and germ cell differentiation via distinct mechanisms. Removal or knock down of dBrel function in the germline or somatic niche cell lineage leads to a gradual GSC loss and disruption of H3K4 trimethylation in the Drosophila ovary. Further studies suggest that the defective GSC maintenance is attributable to compromised BMP signaling emitted from the stem cell niche and impaired adhesion of GSCs to their niche. On the other hand, dBre1-RNAi expression in escort cells causes a loss of H3K4 trimethylation and accumulation of spectrosome-containing single germ cells in the germarium. Reducing dpp or dally levels suppresses the germ cell differentiation defects, indicating that dBrel limits BMP signaling activities for the differentiation control. Strikingly, all phenotypes observed in dBrel mutant ovaries can be mimicked by RNAi-based reduced expression of dSet1, a Drosophila H3K4 trimethylase. Moreover, genetic studies favor that dBrel interacts with dSet1 in controlling GSC maintenance and germ cell differentiation. Taken together, we identify a dBre1/dSet1 -dependent pathway for the H3K4 methylation involved in the cell fate regulation in the Drosophila ovary. (C) 2013 Elsevier Inc. All rights reserved.