Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, 81377 München, Germany.
Institute of Epigenetics and Stem Cells, Helmholtz Zentrum München, 81377 München, Germany; Bioinformatics Unit, Biomedical Center, Ludwig-Maximilians-University, 82152 Planegg-Martinsried, Germany.
Cell Rep. 2022 Dec 27;41(13):111865. doi: 10.1016/j.celrep.2022.111865.
How transcription is regulated as development commences is fundamental to understand how the transcriptionally silent mature gametes are reprogrammed. The embryonic genome is activated for the first time during zygotic genome activation (ZGA). How RNA polymerase II (Pol II) and productive elongation are regulated during this process remains elusive. Here, we generate genome-wide maps of Serine 5 and Serine 2-phosphorylated Pol II during and after ZGA in mouse embryos. We find that both phosphorylated Pol II forms display similar distributions across genes during ZGA, with typical elongation enrichment of Pol II emerging after ZGA. Serine 2-phosphorylated Pol II occurs at genes prior to their activation, suggesting that Serine 2 phosphorylation may prime gene expression. Functional perturbations demonstrate that CDK9 and SPT5 are major ZGA regulators and that SPT5 prevents precocious activation of some genes. Overall, our work sheds molecular insights into transcriptional regulation at the beginning of mammalian development.
在胚胎基因组激活（ZGA）期间，RNA 聚合酶 II（Pol II）和有效的延伸如何被调控仍然难以捉摸。在这里，我们在小鼠胚胎中生成了 ZGA 期间和之后 Serine 5 和 Serine 2 磷酸化 Pol II 的全基因组图谱。我们发现，在 ZGA 期间，两种磷酸化的 Pol II 形式在基因上都显示出相似的分布，在 ZGA 之后出现了典型的延伸富集 Pol II。Serine 2 磷酸化的 Pol II 出现在基因被激活之前，这表明 Serine 2 磷酸化可能为基因表达做好准备。功能扰动表明 CDK9 和 SPT5 是主要的 ZGA 调控因子，而 SPT5 可以防止一些基因过早激活。总的来说，我们的工作为哺乳动物发育早期的转录调控提供了分子见解。
