RRC ID 83492
著者 Guo Y, Kitano T, Inoue K, Murano K, Hirose M, Li TD, Sakashita A, Ishizu H, Ogonuki N, Matoba S, Sato M, Ogura A, Siomi H.
タイトル Obox4 promotes zygotic genome activation upon loss of Dux.
ジャーナル Elife
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 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.
巻・号 13
公開日 2024-6-24
DOI 10.7554/eLife.95856
PII 95856
PMID 38856708
PMC PMC11196112
MeSH Animals Embryonic Development / genetics Gene Expression Regulation, Developmental Genome Homeodomain Proteins* / genetics Homeodomain Proteins* / metabolism Mice Mice, Knockout Zygote* / metabolism
IF 7.08
リソース情報
ヒト・動物細胞 EB3(AES0139)