Maternal Ezh1/2 deficiency in oocyte delays H3K27me2/3 restoration and impairs epiblast development responsible for embryonic sub-lethality in mouse.
Yinan ZhaoDandan BaiYou WuDan ZhangMengying LiuYingpu TianJinhua LuHaibin WangShao-Rong GaoZhongxian LuPublished in: Development (Cambridge, England) (2022)
How maternal Ezh1 and Ezh2 function in H3K27 methylation in vivo in pre-implantation embryos and during embryonic development is not clear. Here, we have deleted Ezh1 and Ezh2 alone or simultaneously from mouse oocytes. H3K27me3 was absent in oocytes without Ezh2 alone, while both H3K27me2 and H3K27me3 were absent in Ezh1/Ezh2 (Ezh1/2) double knockout (KO) oocytes. The effects of Ezh1/2 maternal KO were inherited in zygotes and early embryos, in which restoration of H3K27me3 and H3K27me2 was delayed by the loss of Ezh2 alone or of both Ezh1 and Ezh2. However, the ablation of both Ezh1 and Ezh2, but not Ezh1 or Ezh2 alone, led to significantly decreased litter size due to growth retardation post-implantation. Maternal Ezh1/2 deficiency caused compromised H3K27me3 and pluripotent epiblast cells in late blastocysts, followed by defective embryonic development. By using RNA-seq, we examined crucial developmental genes in maternal Ezh1/2 KO embryos and identified 80 putatively imprinted genes. Maternal Ezh1/2-H3K27 methylation is inherited in offspring embryos and has a critical effect on fetal and placental development. Thus, this work sheds light on maternal epigenetic modifications during embryonic development.
Keyphrases
- long noncoding rna
- long non coding rna
- rna seq
- dna methylation
- birth weight
- gene expression
- genome wide
- pregnancy outcomes
- adipose tissue
- pregnant women
- induced apoptosis
- body mass index
- metabolic syndrome
- cell death
- transcription factor
- physical activity
- atrial fibrillation
- signaling pathway
- insulin resistance
- high fat diet
- gestational age
- smoking cessation
- endoplasmic reticulum stress
- simultaneous determination
- radiofrequency ablation