Abstract
Once fertilized, mouse zygotes rapidly proceed to zygotic genome activation (ZGA), during which long terminal repeats (LTRs) of murine endogenous retroviruses with leucine tRNA primer (MERVL) are potently activated by a conserved homeodomain-containing pioneer factor, DUX. However, Dux-knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by unknown factor(s). In the present study, 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. Single knockdown of Obox4 or Dux is tolerated by embryogenesis, whereas Obox4/Dux double knockdown completely compromises embryonic development. Genome-wide epigenetic profiling revealed that OBOX4 binds to MERVL LTRs as well as murine endogenous retroviruses with lysine tRNA primer (MERVK) LTRs, and mediates the deposition of active histone modifications. Our study identified OBOX4 as a pioneer factor that provides genetic redundancy to pre-implantation development.
Competing Interest Statement
The authors have declared no competing interest.
