Wellcome Trust/Cancer Research United Kingdom Gurdon Institute, University of Cambridge, Cambridge, United Kingdom.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Elife. 2018 May 10;7:e33361. doi: 10.7554/eLife.33361.
Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.
早期的小鼠发育受到染色质修饰动态变化的调控，包括 G9a 介导的组蛋白 H3 赖氨酸 9 二甲基化 (H3K9me2)。之前，我们研究了其在胚胎植入后发育中的作用 (Zylicz 等人，2015 年)。在这里，我们探讨了在受精后不久耗尽卵母细胞中母源遗传的 G9a 对发育的影响。我们发现 G9a 通常在 4 到 8 细胞阶段积累，以促进一组 4 细胞阶段特异性基因的及时抑制。G9a 母源遗传的丧失破坏了基因调控网络，导致晚期囊胚阶段发育延迟和内细胞团谱系不稳定。我们的结果表明，这种母源遗传的表观遗传调节剂在为发育进程创造有利条件以及细胞命运选择方面起着至关重要的作用。
