Obox4 promotes zygotic genome activation upon loss of Dux

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 pr...

Full description

Saved in:
Bibliographic Details
Published in:eLife 2024-06, 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: Article
Language:English
Subjects:
Candidates
Developmental Biology
Embryogenesis
Embryos
Epigenetics
Gene expression
Genomes
Homeobox
Monoclonal antibodies
preimplantation development
Proteins
retrotransposon
Stem cells
Transcription factors
Transfer RNA
tRNA Leu
tRNA Lys
Zygotes
zygotic genome activation
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 2-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 pre-implantation development.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.95856