Metabolic control of histone acetylation for precise and timely regulation of minor ZGA in early mammalian embryos

We report that oxidized nicotinamide adenine dinucleotide (NAD+) is indispensable for mouse pre-implantation development. NAD+ could avoids excessive minor zygotic gene activation (ZGA) by cooperating with SIRT1 to remove zygotic H3K27ac. In human, NAD+ supplement can promote the removal of zygotic H3K27ac and benefit pre-implantation development. Our findings demonstrate that precise and timely regulation of minor ZGA is controlled by metabolic dynamics, and enhance our understanding of the metabolism of mammalian early embryos. Overall design: Examination of H3K27ac in mouse pre-implantation embryos. Examination of RNA-seq in mouse pre-implantation embryos.