Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Kimiko Inoue
Bioresource Engineering Division, Bioresource Center, RIKEN, Tsukuba, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan
Kensaku Murano
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Michiko Hirose
Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan
Ten D Li
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Akihiko Sakashita
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan
Hirotsugu Ishizu
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan
Narumi Ogonuki
Bioresource Engineering Division, Bioresource Center, RIKEN, Tsukuba, Japan
Shogo Matoba
Bioresource Engineering Division, Bioresource Center, RIKEN, Tsukuba, Japan
Bioresource Engineering Division, Bioresource Center, RIKEN, Tsukuba, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan
Department of Molecular Biology, Keio University School of Medicine, Tokyo, Japan; Human Biology Microbiome Quantum Research Center (WPI-Bio2Q), Keio University, Tokyo, Japan
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 activated by a conserved homeodomain-containing transcription factor, DUX. However, Dux-knockout embryos produce fertile mice, suggesting that ZGA is redundantly driven by an unknown factor(s). Here, we present multiple lines of evidence that the multicopy homeobox gene, Obox4, encodes a transcription factor that is highly expressed in mouse two-cell embryos and redundantly drives ZGA. Genome-wide profiling revealed that OBOX4 specifically binds and activates MERVL LTRs as well as a subset of murine endogenous retroviruses with lysine tRNA primer (MERVK) LTRs. Depletion of Obox4 is tolerated by embryogenesis, whereas concomitant Obox4/Dux depletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to preimplantation development.
