Analysis of chromatin landscapes in early human development reveals epigenetic transition during ZGA

ABSTRACT: Upon fertilization, drastic chromatin reorganization occurs during human preimplantation development. However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored. Deciphering such process is crucial for understanding both early human development and in vitro fertilization. Here, we investigated genome-wide chromatin accessibility in human preimplantation embryos by employing an improved ATAC-seq that uses as few as 20 cells. We found widespread accessible chromatin in early human embryos that overlaps extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses showed both conservation and divergence in regulatory circuitry between human and mouse early development, and between naïve human pluripotency in vivo and human embryonic stem cells. Surprisingly, we also found widespread open chromatin at the 2-cell stage despite its minimal transcription activities. Such accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others are located in distal regions enriched for transcription factor binding sites and overlap with partially methylated domains (PMDs) in human oocytes. A large portion of these regions then rapidly become inaccessible upon zygotic genome activation (ZGA). Importantly, such drastic transition of chromatin accessibility during ZGA is well conserved in mouse embryos. Furthermore, it strongly correlates with the reprogramming of non-canonical H3K4me3 (ncH3K4me3), a form of histone mark that is uniquely present in oocytes and pre-ZGA embryos and contributes to genome silencing. Finally, both the reprogramming of chromatin accessibility and ncH3K4me3 during ZGA is completely blocked upon transcription inhibition, indicating a critical role of zygotic transcription in shaping early epigenomes. Together, these data revealed conserved chromatin state transition during ZGA in human and mouse early development.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE101571 | GEO | 2018/05/03

REPOSITORIES: GEO