G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst.

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

doi:10.7554/elife.33361

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.

Highlights

The first developmental events in mouse are subject to regulation by information stored in the oocyte
The process of maternal-to-zygotic transition (MZT) in mice is first initiated in the late zygote, becoming more prominent at 2 cell stage (2C) on embryonic day (E) 1.5 (Golbus et al, 1973; Hamatani et al, 2004; Peaston et al, 2004)
We show that G9a is maternally inherited and drives the accumulation of H3K9me2 at 4C and 8C stage, which accounts for timely repression of a subset of transcripts expressed at 4C

Summary

Introduction

The first developmental events in mouse are subject to regulation by information stored in the oocyte. The initial wave of activation of many genes is followed by their repression within one or two cell cycles (Falco et al, 2007; Hamatani et al, 2004). We show that G9a (encoded by Ehmt gene) is maternally inherited and drives the accumulation of H3K9me at 4C and 8C stage, which accounts for timely repression of a subset of transcripts expressed at 4C. Severe disruption of the gene regulatory network follows upon maternal loss of G9a, resulting in developmental delay and destabilisation of ICM lineages, and frequent loss of embryos at the peri-implantation stage. Our results indicate that maternally-inherited G9a is crucial for regulating appropriate gene expression changes during preimplantation development

Results and discussion

Materials and methods

Funding Funder Wellcome