Histone variant H2A.Z regulates zygotic genome activation

Dafne Ibarra-Morales, Michael Rauer, Piergiuseppe Quarato, Leily Rabbani, Fides Zenk, Mariana Schulte-Sasse, Francesco Cardamone, Alejandro Gomez-Auli, Germano Cecere and Nicola Iovino ()
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Dafne Ibarra-Morales: Max Planck Institute of Immunobiology and Epigenetics
Michael Rauer: Max Planck Institute of Immunobiology and Epigenetics
Piergiuseppe Quarato: Institut Pasteur, Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, UMR3738, CNRS
Leily Rabbani: Max Planck Institute of Immunobiology and Epigenetics
Fides Zenk: Max Planck Institute of Immunobiology and Epigenetics
Mariana Schulte-Sasse: Max Planck Institute of Immunobiology and Epigenetics
Francesco Cardamone: Max Planck Institute of Immunobiology and Epigenetics
Alejandro Gomez-Auli: Max Planck Institute of Immunobiology and Epigenetics
Germano Cecere: Institut Pasteur, Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, UMR3738, CNRS
Nicola Iovino: Max Planck Institute of Immunobiology and Epigenetics

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.

Date: 2021
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DOI: 10.1038/s41467-021-27125-7

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