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Contributions of chromatin remodelling factors CHRAC/ACF to epigenome programming during oogenesis and early embryogenesis in Drosophila melanogaster

染色质重塑因子 CHRAC/ACF 对果蝇卵子发生和早期胚胎发生过程中表观基因组编程的贡献

基本信息

批准号：
66086170
负责人：
Professor Dr. Peter Burkhard Becker
金额：
--
依托单位：
Lehrstuhl Molekularbiologie
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 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/66086170?language=en
关键词：
Contributions chromatin remodelling factors CHRAC

项目摘要

We seek to understand the role of the ISWI-containing chromatin remodelling factors CHRAC/ACF during oogenesis and early embryogenesis in Drosophila melanogaster. We found the signature subunit of these remodellers, ACF1, prominently expressed in the female germ line. ACF1 is enriched in the germ stem cells (GSCs) and in the cystoblasts that originate by asymmetric division from a GSC. High levels of ACF1 mark the cystoblast destined to become the oocyte. Preliminary results suggest that overexpression of ACF1 leads to egg chambers containing multiple oocytes and abnormal numbers of nurse cells. A significant number of egg chambers are not functional in acf1 mutant flies. These and other results may indicate a perturbation of stem cell division programmes. In order to explore the physiological context of ACF1 function we will identify molecular interactors (protein, chromatin binding sites and RNA) during oogenesis and embryogenesis. We already generated critical tools for this endeavour. We biochemically identified a novel interaction of ACF with a Domino-containing nucleosome remodelling complex in early embryos. Since Domino, like ISWI, is involved in stem cell fate during oogenesis we will explore functional and physical interactions of both remodelling complexes during oogenesis.

我们试图了解含有ISWI的染色质重塑因子CHRAC/ACF在果蝇卵子发生和早期胚胎发生中的作用。我们发现这些重塑的标志性亚基ACF 1在女性生殖系中显著表达。ACF 1富集在生殖干细胞（GSC）和成囊细胞中，这些细胞是由GSC的不对称分裂产生的。高水平的ACF 1标志着成囊细胞注定成为卵母细胞。初步结果表明，过量表达的ACF 1导致卵室含有多个卵母细胞和异常数量的护士细胞。在acf 1突变果蝇中，有相当数量的卵室是不起作用的。这些和其他结果可能表明干细胞分裂程序的干扰。为了探索ACF 1功能的生理背景，我们将确定卵子发生和胚胎发生过程中的分子相互作用（蛋白质，染色质结合位点和RNA）。我们已经为这一努力创造了重要工具。我们在早期胚胎中用生物化学方法鉴定了ACF与含有多米诺的核小体重塑复合物的新型相互作用。由于多米诺骨牌，像ISWI，是在卵子发生过程中参与干细胞的命运，我们将探讨功能和物理的相互作用，在卵子发生过程中的重塑复合物。