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 post-zygotically 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.

在合子基因组激活（ZGA）之前，静态基因组经过重新编程以过渡到转录活性状态。然而，尚不清楚早期胚胎发生过程中常染色质建立的机制。在这里，我们表明组蛋白H4赖氨酸16乙酰化（H4K16ac）保持从卵母细胞到果蝇受精的胚胎和哺乳动物。H4K16ac形成大域，可控制果蝇中ZGA之前启动子的核小体可及性。导致H4K16ac丢失的MOF乙酰转移酶的母亲耗竭会导致异常的RNA Pol II募集，损害ZGA期间活性基因组区室的3D组织，并导致后合基因表达基因的下调。组蛋白脱乙酰基酶的种系消耗显示，其他乙酰基标记不能补偿卵母细胞中H4K16ac的丢失。此外，MOF的合子再表达既不能恢复胚胎活力，也不能恢复X染色体剂量补偿。因此，母体H4K16ac为后代提供了指导功能，引发了未来的基因激活。