High-resolution mapping of embryonic genome activation unveils a decoupling of transcription activation from precocious H3K4me3 removal.

Authors

Jasmina Al-Mousawi, Luca Michetti, Laura Castaldi, Na Liu, Laura Villacorta, Vladimir Benes, Ana Boskovic

Published in

Science advances. Volume 12. Issue 32. Pages eaec9545. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

The lack of temporal resolution in transcriptomic data during mammalian embryonic genome activation (EGA) has precluded the comprehensive understanding of the functional relationships between the various gene regulatory mechanisms governing this process. Here, we finely dissect the transcriptional dynamics of mouse EGA using precision in vitro fertilization (IVF) coupled with single-embryo RNA sequencing. Our highly temporally resolved dataset uncovers an extensive, step-wise remodeling of the embryonic messenger RNA landscape, affecting ∼30% of the total detectable transcripts over a 9-hour time frame. We capture the gradual shift from maternal to embryonic messenger RNAs, successfully identify ribosome biogenesis and translation as hallmarks of EGA, and find previously unidentified gene expression dynamics. We further uncover a set of eight histone demethylating enzymes among the earliest up-regulated EGA genes and leverage our precision-IVF to dissect the transcriptional versus developmental impact of histone H3 lysine-4 trimethylation (H3K4me3) remodeling after fertilization. Our results indicate that precocious removal of H3K4me3 from embryonic chromatin only modestly affects embryonic transcription without perturbing EGA timing, arguing against a major instructive role of precocious remodeling of maternally inherited H3K4me3 after fertilization on genome activation. High-resolution transcriptome mapping coupled with functional perturbations allows us to distinguish direct gene expression effects from general impacts on developmental timing, opening avenues for further quantitative characterization of the impact of epigenome remodeling on embryonic transcription.

PMID:
42566531
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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