Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction, Ministry of Education College of Animal Science and Technology, Huazhong Agricultural University, China.
Biol Reprod. 2018 Apr 1;98(4):449-464. doi: 10.1093/biolre/ioy004.
Understanding factors that regulate zygotic genome activation (ZGA) is critical for determining how cells are reprogrammed to become totipotent or pluripotent. There is limited information regarding how this process occurs physiologically in early mammalian embryos. Here, we identify a mediator complex subunit, MED13, as translated during mouse oocyte maturation and transcribed early from the zygotic genome. Knockdown and conditional knockout approaches demonstrate that MED13 is essential for ZGA in the mouse, in part by regulating expression of the embryo-specific chromatin remodeling complex, esBAF. The role of MED13 in ZGA is mediated in part by interactions with E2F transcription factors. In addition to MED13, its paralog, MED13L, is required for successful preimplantation embryo development. MED13L partially compensates for loss of MED13 function in preimplantation knockout embryos, but postimplantation development is not rescued by MED13L. Our data demonstrate an essential role for MED13 in supporting chromatin reprogramming and directed transcription of essential genes during ZGA.
理解调控合子基因组激活（ZGA）的因素对于确定细胞如何被重新编程为全能性或多能性至关重要。关于这个过程在早期哺乳动物胚胎中如何在生理上发生的信息有限。在这里，我们鉴定出一个中介复合物亚基 MED13，它在小鼠卵母细胞成熟过程中被翻译，并在合子基因组中早期转录。敲低和条件敲除方法表明，MED13 在小鼠的 ZGA 中是必不可少的，部分原因是通过调节胚胎特异性染色质重塑复合物 esBAF 的表达。MED13 在 ZGA 中的作用部分是通过与 E2F 转录因子的相互作用介导的。除了 MED13 之外，其同源物 MED13L 对于成功的植入前胚胎发育也是必需的。MED13L 部分补偿了植入前敲除胚胎中 MED13 功能的丧失，但植入后发育不能被 MED13L 挽救。我们的数据表明，MED13 在支持合子基因组激活期间染色质重编程和必需基因的定向转录中具有重要作用。
