Obox4 secures zygotic genome activation upon loss of Dux

We report that the multicopy mouse homeobox gene Obox4 encodes a transcription factor that redundantly drives ZGA. OBOX4 is highly expressed in mouse 2-cell embryos. Obox4 or Dux single knockdown is tolerated by embryogenesis, whereas Obox4/Dux double knockdown completely compromises embryonic development. Genome-wide epigenetic profiling reveals that OBOX4 binds MERVL LTRs and murine endogenous retrovirus with lysine tRNA primer (MERVK) LTRs and mediates deposition of active histone modifications. Overall design: Following data are included in this accession: 1) RNA-seq of Obox4 over-expressed and non-over-expressed mESCs. 2) RNA-seq of scramble knockdown, Obox4 single knockdown, Dux single knockdown, Obox4/Dux double knockdown, and Obox4/Dux double knockdown with Obox4 mRNA rescued mouse 2C-embryos. 3) RNA-seq of scramble knockdown and Obox4/Dux double knockdown mouse morulae. 4) RNA-seq of 2C blastomeres of Dux KO with Obox4 WT/Het/KO genotypes. 5) RNA-seq of PlaB treated WT, Obox4 single knockout, Dux single knockout, and Obox4/Dux double knockout mESCs. 6) CUT&RUN of Obox4 in Obox4 over-expressed mESC, CUT&RUN of Dux in Dux over-expressed mESC. 7) CUT&RUN of H3K4me3, H3K27ac, and H3K27me3 in WT mESCs and Obox4 KO mESCs. 8) CUT&RUN of H3K4me3, H3K27ac, and H3K27me3 in PlaB treated WT mESCs and Obox4 KO mESCs.