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在果蝇卵发生和早期胚胎发生中的作用。我们发现这些重塑分子的标志性亚基ACF1在雌性种系中显著表达。ACF1在生殖干细胞（GSC）和由GSC不对称分裂产生的成囊细胞中富集。高水平的ACF1标志着囊胚注定成为卵母细胞。初步结果表明，ACF1的过表达导致卵室含有多个卵母细胞和异常数量的护理细胞。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程序受到干扰。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、染色质结合位点和RNA）。我们已经为这项努力创造了关键的工具。我们在早期胚胎中生物化学鉴定了ACF与含有多米诺骨牌的核小体重塑复合物的一种新的相互作用。由于多米诺，像ISWI一样，在卵子发生过程中参与了干细胞的命运，我们将探索这两种重塑复合物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.