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Abstract:
Before zygotic genome activation (ZGA), the quiescent genome undergoes reprogramming to transition into
the transcriptionally active state. However, the mechanisms underlying euchromatin establishment during
early embryogenesis remain poorly understood. Here, we show that histone H4 lysine 16 acetylation
(H4K16ac) is maintained from oocytes to fertilized embryos in Drosophila and mammals. H4K16ac forms
large domains that control nucleosome accessibility of promoters prior to ZGA in flies. Maternal depletion
of MOF acetyltransferase leading to H4K16ac loss causes aberrant RNA Pol II recruitment, compromises
the 3D organization of the active genomic compartments during ZGA, and causes downregulation of postzygotically
expressed genes. Germline depletion of histone deacetylases revealed that other acetyl marks
cannot compensate for H4K16ac loss in the oocyte. Moreover, zygotic re-expression of MOF was neither
able to restore embryonic viability nor onset of X chromosome dosage compensation. Thus, maternal H4K16ac provides an instructive function to the offspring, priming future gene activation.
