<i>Obox4</i> promotes zygotic genome activation upon loss of <i>Dux</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38856708.
- Also identified by DOI 10.7554/eLife.95856 and PMC identifier 11196112.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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, <i>Dux</i>-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, <i>Obox4</i>, 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 <i>Obox4</i> is tolerated by embryogenesis, whereas concomitant <i>Obox4</i>/<i>Dux</i> depletion markedly compromises embryonic development. Our study identified OBOX4 as a transcription factor that provides genetic redundancy to preimplantation development.
Medical subject headings
- Homeodomain Proteins
- Zygote