Stage-specific H3K9me3 occupancy ensures retrotransposon silencing in human pre-implantation embryos

H3K9me3, as a hallmark of heterochromatin, is important for cell-fate specification. However, it remains un-known how H3K9me3 is reprogrammed during human early embryo development. Here, we profiled genome-wide H3K9me3 in human oocytes and early embryos and discovered stage-specific H3K9me3 deposition on long terminal repeats (LTRs) at the 8-cell and blastocyst stages. We found that 8-cell-specific H3K9me3 was temporarily established in enhancer-like regions, whereas blastocyst-specific H3K9me3 was more stable. DUX and multiple Kru???ppel-associated box domain zinc finger proteins(KRAB-ZNFs) were identified as poten-tial factors for establishing 8C-and blastocyst-specific H3K9me3, respectively. Intriguingly, our analysis showed that stage-specific H3K9me3 allocation was attenuated by either Dux knockout orZfp51 knockdown in mouse early embryos. Moreover, we observed the existence of H3K4me3/H3K9me3 and H3K4me3/ H3K27me3 bivalent chromatin domains in human blastocysts, priming for lineage differentiation. Together, our data unveil that the epigenetic switch from DNA methylation to H3K9me3 ensures the precise regulation of retrotransposons in human pre-implantation embryos.

Automated summary

The deposition of H3K9me3 in human oocytes and early embryos has been found to be stage-specific, with enhancer-like regions being temporarily established during the 8-cell stage and greater stability during the blastocyst stage. The genes DUX and KRAB-ZNFs have been identified as potential factors involved in the establishment of stage-specific H3K9me3. Furthermore, the presence of bivalent chromatin domains in human blastocysts suggests priming for lineage differentiation.