The dynamic reprogramming of H3K9me3 at hominoid-specific retrotransposons during early human development

Reprogramming of H3K9me3-dependent heterochromatin is required for early development. How H3K9me3 is involved in early human development is, however, largely unclear. Here, we resolve the temporal landscape of H3K9me3 during human preimplantation development and its regulation for diverse hominoid-specific retrotransposons. At the 8-cell stage, H3K9me3 reprogramming at hominoid-specific retrotransposons termed SINE-VNTR-Alu (SVA) facilitates interaction between certain promoters and SVA-derived enhancers, facilitating the zygotic genome activation. In trophectoderm, de novo H3K9me3 domains prohibit pluripotent transcription factors from binding on hominoid-specific retrotransposons-derived regulatory elements for inner cell mass (ICM)-specific genes. H3K9me3 re-establishment at SVA elements in ICM is associated with higher transcription of DNA damage repair genes, compared to naïve human pluripotent stem cells. Our data demonstrate that species-specific reorganization of H3K9me3-dependent heterochromatin at hominoid-specific retrotransposons plays important roles during early human development, shedding light on how the epigenetic regulatory network for early development has evolved in mammals. Overall design: We investigated 1) H3K9me3 landscape on the genome of human preimplantation embryos using advanced ultra-low input ChIP-seq (AULIChIP-seq). AULIChIP-seq was performed in two biological replicates of human 4-cell embryo, 8-cel embryo, morula, inner cell mass (ICM) and trophectoderm (TE). 2) H3K9me3 or H3K27me3 landscape on the genome of hESCs and hTSCs using advanced ultra-low input ChIP-seq (AULIChIP-seq) or conventional ChIP-seq. AULIChIP-seq was performed in two biological replicates of hTSCs. 3) transcriptome of abnormal human embryos using SMART-seq2. 4) We investigated H3K9me3 landscape and gene expression of hESCs, prEpiSC and human preimplantation embryos in which the H3K9me3 modification were deposited on SVAs by epigenetic editing system (dCas9-KRAB). 5) genome of abnormal human embryos using WGS.