G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

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 H3K9me2 normally accumulates at 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 conductive conditions for developmental progression and on cell fate choices. Single embryo RNAseq was performed at E2.5 8-cell stage from 10 control and 10 maternally depleted Ehmt2 embryos.