O-058 Metabolism, histone modification and early embryo development

Abstract

Abstract Cellular metabolism provides fundamental components for chromatin dynamics and epigenetics. However, metabolic features, and their impact on epigenetic remodeling during mammalian pre-implantation development, remain poorly understood. In this study, we established the metabolic landscape of mouse pre-implantation embryos from zygote to blastocyst, and quantified their absolute carbohydrate metabolites. We found that amino acid/carbohydrate/lipid metabolism increased during pre-implantation development, whereas nucleotide metabolism increased at the 4- and 8-cell stages. We further demonstrated that oxidized nicotinamide adenine dinucleotide (NAD+) is indispensable for mouse pre-implantation development. Mechanistically, NAD+ avoids excessive minor zygotic gene activation (ZGA) by cooperating with deacylase SIRT1 to remove zygotic H3K27ac. In human, NAD+ supplement can promote the removal of zygotic H3K27ac and benefit preimplantation 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.