An integrated chromatin accessibility and transcriptome landscape of human pre-implantation embryos

The human pre-implantation development involves extensive changes in chromatin structure and transcriptional activity. Here, by developing LiCAT-seq, a technique enabling simultaneous profiling of chromatin accessibility and gene expression with ultra-low input of cells, we mapped the chromatin accessibility and transcriptome landscapes for human pre-implantation embryos. We observed global difference in chromatin accessibility between sperm and all stages of embryos, finding that the accessible regions in sperm tend to occur in gene-poor genomic regions. Integrative analyses between the two omics layers revealed strong association between the establishment of accessible chromatin and embryo genome activation (EGA), and uncovered transcription factors and endogenous retrovirus (ERVs) specific to EGA. In particular, a large proportion of the early activated genes and ERVs are bound by DUX4 and become accessible as early as the 2- to 4-cell stages. Our results thus offer new mechanistic insights into the molecular events inherent to human pre-implantation development.