No abstract

Highlights d The DHS landscape is gradually established during human embryo development d OCT4 contributes to zygotic genome activation in humans, but not in mice d Younger genes establish DHS at later stages, and older genes show the opposite trend d Human transposons SVA/HERVK harbor DHSs and are specifically expressed in embryos

Translational regulation plays a critical role during the oocyte-to-embryo transition (OET) and zygotic genome activation (ZGA). Here, we integrated ultra-low-input Ribo-seq with mRNA-seq to co-profile the translatome and transcriptome in human oocytes and early embryos. Comparison with mouse counterparts identified widespread differentially translated genes functioning in epigenetic reprogramming, transposon defense, and small RNA biogenesis, in part driven by species-specific regulatory elements in 3′ untranslated regions. Moreover, PRD-like homeobox transcription factors, including TPRXL, TPRX1, and TPRX2, are highly translated around ZGA. TPRX1/2/L knockdown leads to defective ZGA and preimplantation development. Ectopically expressed TPRXs bind and activate key ZGA genes in human embryonic stem cells. These data reveal the conservation and divergence of translation landscapes during OET and identify critical regulators of human ZGA.