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Obox4 promotes zygotic genome activation upon loss of Dux .

Youjia GuoTomohiro KitanoKimiko InoueKensaku MuranoMichiko HiroseTen D LiAkihiko SakashitaHirotsugu IshizuNarumi OgonukiShogo MatobaMasayuki SatoAtsuo OguraHaruhiko Siomi
Published in: eLife (2024)
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.
Keyphrases
  • transcription factor
  • genome wide
  • genome wide identification
  • dna methylation
  • single cell
  • dna binding
  • copy number
  • metabolic syndrome
  • cell therapy
  • adipose tissue
  • bone marrow
  • amino acid