原始卵泡维持、卵泡生长和“母体-胚胎转换”过程，是雌性生殖的关键调控环节，也是研究表观遗传调控的理想模型。目前还不清楚组蛋白H3第9位赖氨酸（H3K9）甲基化修饰对卵母细胞各发育阶段基因表达的动态平衡和染色质构象转变有何生理调节意义。申请人近年来发现，CRL4泛素连接酶对卵母细胞发育至关重要，并找到在进化过程中高度保守的、卵子发生所必需的底物识别蛋白DCAF13。初步研究显示，DCAF13可能通过泛素化降解H3K9甲基转移酶SUV39H1/2，调节卵母细胞基因组的转录活性和染色质构象改变，维持雌性生殖功能。本项目以卵母细胞特异性Dcaf13基因敲除小鼠为模型，研究DCAF13及其底物SUV39H1/2在原始卵泡维持和激活、卵泡生长和排卵、受精后母体胚胎转换过程中的生理功能和生化调节机制，并通过微量样本的基因组学研究，阐明CRL4-DCAF13对各时期卵母细胞转录组和组蛋白甲基化组的影响。

Primordial follicle maintenance, follicle growth, and maternal-zygotic transition processes are key regulated events of female reproduction. These processes are also ideal in vivo model to study epigenetic regulations. The physiological roles of histone H3 trimethylation at lysine 9 (H3K9me3) in regulating balanced gene expression and chromosome configuration changes during oocyte development were insufficiently studied. The recent investigations of our laboratory showed that cullin ring finger ligase-4 (CRL4) complex is crucial for oocyte development. We also identified DCAF13 as a highly conserved novel substrate adaptor protein of CRL4. Our preliminary results suggested that DCAF13 is required for oogenesis from C. elegans to mouse. In mammalian cells, DCAF13 may regulate oocyte genome transcription activity and chromosome configuration changes by mediating the poly-ubiquitination and degradation of SUV39H1/2, the key histone H3 trimethylases. In this study we aim to investigate the functions and regulations of maternal DCAF13 and its substrate SUV391/2 during primordial follicle maintenance, follicle activation and growth, ovulation, and maternal-zygotic transition. We will also elucidate the influence of CRL4-DCAF13 on oocyte transcriptomes and histone methylomes at various developmental stages of oogenesis and early embryo development.