DNA methylation, chromatin states and their interrelationships represent critical epigenetic information, but these are largely unknown in human early embryos. Here, we apply single-cell chromatin overall omic-scale landscape sequencing (scCOOL-seq) to generate a genome-wide map of DNA methylation and chromatin accessibility at single-cell resolution during human preimplantation development. Unlike in mice, the chromatin of the paternal genome is already more open than that of the maternal genome at the mid-zygote stage in humans, and this state is maintained until the 4-cell stage. After fertilization, genes with high variations in DNA methylation, and those with high variations in chromatin accessibility, tend to be two different sets. Furthermore, 1,797 out of 5,155 (35%) widely open chromatin regions in promoters closed when transcription activity was inhibited, indicating a feedback mechanism between transcription and open chromatin maintenance. Our work paves the way for dissecting the complex, yet highly coordinated, epigenetic reprogramming during human preimplantation development.

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(Abstracted from Nat Cell Biol 2018;20:847–858) DNA methylation and chromatin states are critical epigenetic indicators in embryogenesis that have been extensively studied during mouse preimplantation development. DNA methylation dynamics and parental allele-specific DNA methylation in human preimplantation embryos have been analyzed thoroughly; however, chromatin remodeling, parental allele-specific chromatin accessibility, and interrelationships between these omics are not well understood.