The E2 SUMO-conjugating enzyme UBE2I is essential for chromatin dynamics and transcriptional silencing in mouse oocytes

In mammals, meiotically competent oocytes develop cyclically during ovarian folliculogenesis. During their development, prophase I arrested oocytes are highly transcriptionally active in preparation for the resumption of meiosis and early stages of embryogenesis prior to the maternal to zygotic transition. Defective oocyte development during folliculogenesis leads to meiotic defects, aneuploidy, follicular atresia, or non-viable embryos. SUMOylation, a dynamic post-translational protein modification, is essential for oocyte development during folliculogenesis and to regulate meiotic maturation in mice. We generated a novel oocyte-specific knockout of Ube2i, the sole SUMO E2 ligase, to test its role growing ovarian follicles using Zp3-cre. Ube2i Zp3-cre+ female mice are sterile with oocytes with defects in meiotic progression but not meiotic resumption. Importantly, fully grown oocytes do not silence transcription and prematurely activate the zygotic transcriptional program. This work uncovers unknown functions of UBE2i as a key orchestrator of chromatin and transcriptional regulation in oocytes. We performed RNA-sequencing analysis on 17 individual control and 17 individual Ube2i cKO oocytes在哺乳动物中，具备减数分裂能力的卵母细胞在卵巢卵泡发生过程中周期性发育。在其发育进程中，停滞在减数分裂I前期的卵母细胞具有高度活跃的转录活性，为减数分裂恢复以及母源-合子转换（maternal to zygotic transition）之前的胚胎发育早期阶段做好准备。卵泡发生过程中卵母细胞发育异常会引发减数分裂缺陷、非整倍体、卵泡闭锁或不可存活胚胎。SUMO化修饰（SUMOylation）作为一种动态的蛋白质翻译后修饰，在小鼠的卵泡发生过程中对卵母细胞发育以及减数分裂成熟的调控至关重要。我们利用Zp3-Cre构建了新型卵母细胞特异性敲除Ube2i的模型——Ube2i是唯一的SUMO E2连接酶，以此探究其在卵巢卵泡生长过程中的作用。Ube2i Zp3-Cre+ 雌性小鼠不育，其卵母细胞存在减数分裂进程缺陷，但减数分裂恢复过程未受影响。值得注意的是，完全成熟的卵母细胞并未沉默转录，反而提前激活了合子转录程序。本研究揭示了UBE2i此前未被发现的功能：其作为卵母细胞中染色质与转录调控的关键枢纽因子。我们对17个对照组卵母细胞与17个Ube2i条件性敲除（cKO）卵母细胞开展了RNA测序（RNA-sequencing）分析。