Life begins with a switch in genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA). Despite its importance, the essential regulators of ZGA remain largely unknown in mammals. Based on de novo motif searches, we identified the orphan nuclear receptor Nr5a2 as a key activator of major ZGA in mouse 2-cell embryos. Nr5a2 is required for progression beyond the 2-cell stage. It binds to its motif within SINE B1/Alu retrotransposable elements found in cis -regulatory regions of ZGA genes. Chemical inhibition suggests that 72% of ZGA genes are regulated by Nr5a2 and potentially other orphan nuclear receptors. Nr5a2 promotes chromatin accessibility during ZGA and binds nucleosomal DNA in vitro. We conclude that Nr5a2 is an essential pioneer factor that regulates ZGA.

中文翻译：

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全能先驱因子 Nr5a2 激活合子基因组

生命始于在合子基因组激活 (ZGA) 期间从母体基因组到胚胎基因组的遗传控制转换。尽管它很重要，但 ZGA 的基本监管机构在哺乳动物中仍然很大程度上未知。基于从头基序搜索，我们将孤儿核受体 Nr5a2 鉴定为小鼠 2 细胞胚胎中主要 ZGA 的关键激活剂。Nr5a2 是超过 2 细胞阶段的进展所必需的。它绑定到其内部的主题正弦 B1/铝逆转录转座元件发现于顺式-ZGA 基因的调控区域。化学抑制表明 72% 的 ZGA 基因受 Nr5a2 和其他潜在的孤儿核受体调节。Nr5a2 在 ZGA 期间促进染色质可及性并在体外结合核小体 DNA。我们得出结论，Nr5a2 是调节 ZGA 的重要先驱因子。