Initiation and epigenetic stability of gene silencing in Drosophila

果蝇基因沉默的启动和表观遗传稳定性

• 批准号: 5391690
• 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: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5391690?language=en
• 关键词: Initiation; epigenetic; stability; gene; silencing

Heterochromatin-induced gene silencing is initiated by the histone H3-K9 methyltransferase SU(VAR)3-9 early in development and stable transmitted over consecutive cell divisions. One central aim of our studies consists in identification of chromatin functions controlling epigenetic maintenance of heterochromatic gene silencing. Strong dosage effects of SU(VAR)3-9 allow to study epigenetic stability of heterochromatic gene silencing by FLIP/FRT dependent mitotic recombination for both the non-silencing suppressed and the enhanced silenced status of the withe gene in the wm4 PEV rearrangement. Based on precise determination of the time in development when SU(VAR)3-9 dependent gene silencing is initiated and its epigenetic stability established, genetic dissection of the underlying control process will be performed by transgene analysis, FLIP/FRT based mutation screens and tests of the over 500 available PEV modifier mutations. In the genetic tests mutations can be identified which interfere with epigenetic initiation or maintenance of heterochromatic gene silencing. Molecular analysis of the identified genes and their products allows identification of the yet unknown molecular processes involved in initiation and maintenance of epigenetic programs as well as to identify experimental tools for reprogramming.

异染色质诱导的基因沉默在发育早期由组蛋白H3-K9甲基转移酶SU(VAR)3-9启动，并在连续的细胞分裂中稳定传播。我们研究的一个中心目标是鉴定控制异色基因沉默的表观遗传维持的染色质功能。在wm4 PEV重排中，SU(VAR)3-9的强剂量效应可以研究FLIP/FRT依赖性有丝分裂重组对withe基因非沉默抑制和增强沉默状态的异色基因沉默的表观遗传稳定性。在精确确定SU(VAR)3-9依赖基因沉默开始的发育时间及其表观遗传稳定性的基础上，将通过转基因分析、基于FLIP/FRT的突变筛选和500多个可用PEV修饰子突变的测试来进行潜在控制过程的遗传解剖。在基因测试中，可以识别干扰表观遗传启动或维持异色基因沉默的突变。对已识别的基因及其产物进行分子分析，可以识别未知的分子过程，这些过程涉及表观遗传程序的启动和维持，以及确定重编程的实验工具。