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

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。我们发现这些重构体的特征亚基ACF1在雌性生殖系中显著表达。ACF1富含于生殖细胞(GSCs)和来源于GSC的不对称分裂的成囊细胞中。高水平的ACF1标志着成囊细胞注定要成为卵母细胞。初步结果表明，ACF1的过度表达导致卵室内含有多个卵母细胞和异常数量的哺乳细胞。在acf1突变果蝇中，有相当数量的卵室不起作用。这些和其他结果可能表明干细胞分裂计划受到干扰。为了探索ACF1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因子(蛋白质、染色质结合部位和RNA)。我们已经为这一努力生成了关键工具。我们在早期胚胎中生化鉴定了ACF与含有Domino的核小体重塑复合体之间的一种新的相互作用。由于Domino和ISWI一样，参与了卵子发生过程中干细胞的命运，我们将探索两种重塑复合体在卵子发生过程中的功能和物理相互作用。

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.