G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

G9a 调节胚泡中的暂时植入前发育程序和谱系分离

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作者:Jan J Zylicz #, Maud Borensztein #, Frederick Ck Wong, Yun Huang, Caroline Lee, Sabine Dietmann, M Azim Surani

Abstract

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.

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