Abstract
Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of enhancer of zeste homolog 2 (EZH2)-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in cell cycle regulation, germline development and embryogenesis. Notably, the H3K9me2 modification extends to active enhancer elements where it promotes developmentally-linked gene silencing and directly marks promoters and gene bodies. This epigenetic mechanism is important for priming gene regulatory networks for critical cell fate decisions in rapidly proliferating postimplantation epiblast cells.
Highlights
Mammalian development progresses through a series of landmark events that are regulated by transcriptional and epigenetic mechanisms
We investigated the dynamics of epigenetic programming of repressive H3K9me2 during early mouse development
We investigated the role of G9a in regulating transposable elements (TEs) as previous studies have shown that loss of G9a in sESC leads to aberrant expression of murine endogenous retroviruses with leucine tRNA primer (MERV-L) (Maksakova et al, 2013)
Summary
Mammalian development progresses through a series of landmark events that are regulated by transcriptional and epigenetic mechanisms. Subsequent development of the ICM leads to the formation of primed postimplantation epiblast cells by E5.5–6.25, which are poised to initiate lineage-specification. This developmental transition is accompanied by epigenetic programming, including genome-wide de novo DNA methylation, and potentially accumulation of histone H3 lysine 9 dimethylation (H3K9me2) and redistribution of histone H3 lysine 27 trimethylation (H3K27me3) (Figure 1A) (Borgel et al, 2010; Leitch et al, 2013; Marks et al, 2012). The precise contribution of epigenetic programming for setting and regulating the transcriptional circuitry in early development remains to be fully elucidated (Li et al, 1992; O’Carroll et al, 2001; Okano et al, 1999; Tachibana et al, 2002)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
