Chimeric PRMT6 protein produced by an endogenous retrovirus promoter regulates cell fate decision in mouse preimplantation embryos

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 ( Prmt6 ) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of MERVL, and is translated into an elongated chimeric protein (PRMT6 MT2B2 ) whose function differs from that of the canonical PRMT6 protein (PRMT6 CAN ) in mouse preimplantation embryos. Overexpression of PRMT6 CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6 MT2B2 increased only H2AR3me2a. In addition, overexpression of PRMT6 MT2B2 in one blastomere of mouse two-cell embryos promoted cell proliferation and differentiation of the blastomere into epiblast cells at the blastocyst stage, while overexpression of PRMT6 CAN repressed cell proliferation. This is the first report of the translation of a chimeric protein (PRMT6 MT2B2 ) in mouse preimplantation embryos. Our results suggest that analyzing chimeric transcripts with MERVL will provide insight into the relationship between zygotic genome activation and subsequent intra- and extra-cellular lineage determination.