Dynamic reprogramming of H3K9me3 at hominoid-specific retrotransposons during human preimplantation development

Jichang Wang

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Reprogramming of H3K9me3-dependent heterochromatin is required for early development. How H3K9me3 is involved in early human development remains, 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, promoting the zygotic genome activation. In trophectoderm, de novo H3K9me3 domains prevent pluripotent transcription factors from binding to hominoid-specific retrotransposons-derived regulatory elements for inner cell mass (ICM)-specific genes. H3K9me3 re-establishment at SVA elements in the ICM is associated with higher transcription of DNA repair genes, when compared with naive 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 regulation for early development has evolved in mammals.
Original languageEnglish
Article numberE12
Pages (from-to)1031-1050
Number of pages20
JournalCell Stem Cell
Issue number7
Publication statusPublished - 7 Jul 2022

Bibliographical note

This research is supported by grants from the National Key R&D Program of China (2018YFA0107000 to L.L. and 2018YFA0108301 to J.W.), the National Natural Science Foundation of China (31871444 to J.W.), the Natural Science Foundation of Guangdong (2021A1515010537 to J.W.), and the Guangdong Introducing Innovative and Entrepreneurial Team Program (2016ZT06S029 to J.W.).


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