Mediator complex component MED13 regulates zygotic genome activation and is required for postimplantation development in the mouse
Mediator complex component MED13 regulates zygotic genome activation and is required for postimplantation development in the mouse
复制标题
介体复合体成分 MED13 调节合子基因组激活，是小鼠植入后发育所必需的。
DOI：
10.1093/biolre/ioy004
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发表时间：
2018-04-01
影响因子：
3.6
通讯作者：
Williams, Carmen J.
中科院分区：
文献类型：
--
作者：
Miao, Yi-Liang;Gambini, Andres;Williams, Carmen J.
了解合子基因组激活（ZGA）的调控因子对于确定细胞如何重编程成为全能或多能性至关重要。关于这一过程在早期哺乳动物胚胎中生理学上如何发生的信息有限。在这里，我们确定了一个调解人复合物亚基，MED13，在小鼠卵母细胞成熟和转录早期从合子基因组翻译。敲除和条件性敲除方法表明，MED13是必不可少的ZGA在小鼠中，部分通过调节胚胎特异性染色质重塑复合物，esBAF的表达。MED13在ZGA中的作用部分通过与E2F转录因子的相互作用介导。除了MED13，它的副产物MED13L是成功的植入前胚胎发育所必需的。MED13 L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MED13 L挽救。我们的数据证明了MED13在ZGA期间支持染色质重编程和必需基因的定向转录中的重要作用。
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.Summary SentenceMED13 is required for activating transcription of essential genes during the maternal to zygotic transition in the mouse.