H4K20me3 erasure facilitates reprogramming to totipotent-like state by promoting DUX4 mediated transcription [ChIP-Seq]
Epigenetic remodeling following fertilization is essential for the acquisition of embryonic totipotency. The role of H4K20me3, a key component epigenetic mark, remains largely unexplored in the context of early human embryogenesis. Here, we observed a dynamic erasure of H4K20me3 modification during zygotic genome activation (ZGA), followed by a re-establishment after ZGA in human embryos. Using in vitro reprogramming of totipotent-like states, we demonstrated transient removal of H4K20me3 in human embryonic stem cells (hESCs) promotes DUX4-mediated expression of totipotent genes, the transition into a totipotent-like state. Mechanistically, we show that H4K20me3 preferentially accumulates around genes specific to 8-cell-like (8CLC) state, which are induced by DUX4 and repressed by H4K20me3 modification. Furthermore, H4K20me3 enrichment near the pericentromeric regions may regulate satellite repeat transcripts, thereby modulating heterochromatin structure to facilitate totipotency reprogramming. Overall design: ChIP-seq of H4K20me3 in hESCs