De novo programming: establishment of epigenome in mammalian oocytes

Abstract Innovations in ultrasensitive and single-cell measurements enable us to study layers of genome regulation in view of cellular and regulatory heterogeneity. Genome-scale mapping allows to evaluate epigenetic features and dynamics in different genomic contexts, including genebodies, CpG islands, imprinting control regions, promoters, partially methylated domains, and repetitive elements. The epigenome of early embryos, fetal germ cells, and sperms has been extensively studied for the past decade, whereas oocytes remain less clear. Emerging evidence now supports the notion that transcription and chromatin accessibility precede de novo DNA methylation in both human and mouse oocytes. Recent studies have also started to chart correlations among different histone modifications and DNA methylation. We discuss the potential mechanistic hierarchy that shapes the oocyte DNA methylome, also providing insights into the convergent and divergent features between humans and mice.