Epigenetic control of pluripotency in Drosophila primordial and ovarian germ line stem cells

果蝇原始和卵巢生殖系干细胞多能性的表观遗传控制

• 批准号: 66107286
• 负责人: Professor Dr. Gunter Reuter (†)
• 金额: --
• 依托单位: Abteilung Entwicklungsgenetik
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/66107286?language=en
• 关键词: Epigenetic; control; pluripotency; Drosophila; primordial

Analysis of histone modification marks revealed specific epigenetic processes in PGCs and GSCs. Like in blastoderm also in PGCs chromatin differentiation is polar. H3K4me1 and H3K27me2/me3 are abundant and the SU(VAR)3-3 demethylase ensures a low level of H3K4me2 in PGCs. Su(var)3-3 mutations impair stemness and development of GSCs. The heterochromatic H3K9me2/me3 marks are controlled by SETDB1 in PGCs and by SU(VAR)3-9 and SETDB1 in GSCs. Abundant chromatin proteins in PGCs are SU(VAR)3-3 and SU(VAR)2-1 associating into an early chromatin protein complex. SU(VAR)2-1 is a novel factor essential for PGC and GSC development. Chromatin differentiation in PGCs is under control of ecdysone signaling. Genetic dissection of gene silencing in germ line stem cells revealed complex epigenetic programming and proved the function of many known epigenetic factors in these processes. In our future work we will focus on defining and functional analysis of epigenetic factors which control histone modifications in germ line stem cells. In our analysis of epigenetic processes in germ line stem cells we will combine genetic techniques with ChIP analysis of germ line chromatin.

组蛋白修饰标记的分析揭示了PGCs和GSCs的特定表观遗传过程。和胚皮细胞一样，PGCs的染色质分化是极性的。H3K4me1和H3K27me2/me3是丰富的，SU(VAR)3-3去甲基化酶确保了PGCs中H3K4me2的低水平。Su(var)3-3突变损害GSCs的干性和发育。异色H3K9me2/me3标记在PGCs中由SETDB1控制，在GSCs中由SU(VAR)3-9和SETDB1控制。PGCs中丰富的染色质蛋白是SU(VAR)3-3和SU(VAR)2-1结合成早期染色质蛋白复合物。SU(VAR)2-1是PGC和GSC发展中必不可少的新因子。PGCs的染色质分化受蜕皮激素信号的控制。生殖系干细胞基因沉默的遗传解剖揭示了复杂的表观遗传编程，并证明了许多已知的表观遗传因子在这些过程中的作用。在我们未来的工作中，我们将重点研究控制生殖系干细胞组蛋白修饰的表观遗传因子的定义和功能分析。在我们对生殖系干细胞的表观遗传过程的分析中，我们将把遗传技术与生殖系染色质的ChIP分析结合起来。