New Nature Communications paper: Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development

Madeleine Fosslie
Madeleine Fosslie

Madeleine Fosslie, researcher in the Genome and Epigenome Regulation in Embryo Development, Ageing and Disease group at the Department of Microbiology, and Erkut Ilaslan, researcher at University of Copenhagen, are first authors on this Nature Communications paper. This study sheds light on the fundamental biology of how the genome is restructured and reprogrammed during the transition from egg to early embryo.

DNA organization in embryo development

This study examines how DNA is organized and regulated in mouse egg cells and very early embryos by following a protein called H2A.Z, one of the proteins around which DNA is wrapped inside the cell. 

The authors show that specific patterns of H2A.Z are established in the egg and passed on to the embryo after fertilization, which could help guide normal embryo development. 

Overall, the work sheds light on the fundamental biology of how the genome is restructured and reprogrammed during the transition from egg to early embryo.

Paper abstract

Epigenomes of mammalian oocytes and embryos undergo major transitions essential for successful development. Here, we provide genome-wide maps of histone variant H2A.Z during twelve stages of mouse oogenesis and preimplantation embryo development and relate it to histone marks and genomic features. This revealed that major waves of H2A.Z incorporation occur early in growing oocytes, forming distinct patterns of maternal, embryonic, and persistent H2A.Z enrichment. 

Late maternal enrichment is inherited by the zygote and precedes reduced formation of lamina associated domains and early replication in the maternal genome of 2-cell embryos. Persistent H2A.Z enrichment is strongly associated with CpG islands and H3K4me3 near transcription start sites of active genes, but thousands of maternal and embryonic H2A.Z incorporation sites exist elsewhere, frequently at transposable elements. 

The persisting H2A.Z enrichments across related developmental stages enable preservation of epigenetic information despite major concurrent changes in H3K4me3, H3K27me3, and DNA methylation. Altogether, this advances our understanding of how histone variants contribute to epigenetic reprogramming during mammalian oogenesis and early development.

Links:

The Nature Communications paper:
Fosslie M, Ilaslan E, Skuland T, Choudalakis M, Søegaard M, Halliwell JA, Khan S, Indahl M, Vera-Rodriguez M, Manaf A, Geijer-Simpson AV, Suganthan R, Jermstad I, Dalen KT, Eskeland R, Kommisrud E, Klungland A, Bjørås M, Fedorcsak P, Greggains GD, Zagrobelny M, Dahl JA, Lerdrup M (2025)
Major waves of H2A.Z incorporation during mouse oogenesis and preimplantation embryo development
Nat Commun, 17 (1), 210
DOI 10.1038/s41467-025-66919-x, PubMed 41331258

The Genome and Epigenome Regulation in Embryo Development, Ageing and Disease research group, headed by John Arne Dahl

Madeleine Fossli - contact information and publications

Erkut Ilaslan (cresco.uio.no)

Department of Microbiology

Centre for Embryology and Healthy Development (CRESCO) - Health in the earliest stage of life (cresco.uio.no)