Obox4 promotes zygotic genome activation upon loss of Dux

• Published in: eLife Vol. 13
• Main Authors: Guo, Youjia, Kitano, Tomohiro, Inoue, Kimiko, Murano, Kensaku, Hirose, Michiko, Li, Ten D, Sakashita, Akihiko, Ishizu, Hirotsugu, Ogonuki, Narumi, Matoba, Shogo, Sato, Masayuki, Ogura, Atsuo, Siomi, Haruhiko
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 24-06-2024; eLife Sciences Publications, Ltd
• Subjects: Animals; Candidates; Developmental Biology; Embryogenesis; Embryonic Development - genetics; Embryos; Epigenetics; Gene expression; Gene Expression Regulation, Developmental; Genome; Genomes; Homeobox; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Mice; Mice, Knockout; Monoclonal antibodies; preimplantation development; Proteins; retrotransposon; Stem cells; Transcription factors; Transfer RNA; tRNA Leu; tRNA Lys; Zygote - metabolism; Zygotes; zygotic genome activation; mouse; transcription factors; developmental biology; preimplantation development; homeobox; retrotransposon; zygotic genome activation
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.95856

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,
-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,
, 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
is tolerated by embryogenesis, whereas concomitant
/
depletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to preimplantation development.