Description
We use rAPOBEC-XTEN-Cas9n-UGI (BE3) to introduce a point mutation (R17H) into 8 loci of Hist1H3 by a single sgRNA and a pre-stop codon into Carm1 in early mouse embryo, and both strategies resulted in developmental defects in pre-implantation embryos and fetal stages with smaller or developmental-delayed embryos. Transcriptomic analysis revealed that Yap1 and cell cycle signaling pathways were dysregulated in Carm1 pre-stop and H3R17H embryos, and Yap1 overexpression could rescue the developmental defects. Our results establish the direct regulatory relationship between Carm1-mediated site-specific histone modifications and mouse embryo development, and we also demonstrate that Hippo-Yap1 acts downstream of Carm1-mediated H3R17me2a to regulate the embryonic development and size determination. Overall design: Examination of RNA expression profiles of E4.5 WT/H3R17H/Carm1-/- mouse embryos by deep sequencing.