Reprogramming of H3K9me3-dependent heterochromatin during mammalian embryo development

Nat Cell Biol. 2018 May;20(5):620-631. doi: 10.1038/s41556-018-0093-4. Epub 2018 Apr 23.

Abstract

H3K9me3-dependent heterochromatin is a major barrier of cell fate changes that must be reprogrammed after fertilization. However, the molecular details of these events are lacking in early embryos. Here, we map the genome-wide distribution of H3K9me3 modifications in mouse early embryos. We find that H3K9me3 exhibits distinct dynamic features in promoters and long terminal repeats (LTRs). Both parental genomes undergo large-scale H3K9me3 reestablishment after fertilization, and the imbalance in parental H3K9me3 signals lasts until blastocyst. The rebuilding of H3K9me3 on LTRs is involved in silencing their active transcription triggered by DNA demethylation. We identify that Chaf1a is essential for the establishment of H3K9me3 on LTRs and subsequent transcriptional repression. Finally, we find that lineage-specific H3K9me3 is established in post-implantation embryos. In summary, our data demonstrate that H3K9me3-dependent heterochromatin undergoes dramatic reprogramming during early embryonic development and provide valuable resources for further exploration of the epigenetic mechanism in early embryos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blastocyst / metabolism*
  • Cell Line
  • Cellular Reprogramming*
  • Chromatin Assembly Factor-1 / genetics
  • Chromatin Assembly Factor-1 / metabolism
  • Chromatin Assembly and Disassembly*
  • DNA Methylation*
  • Embryo Culture Techniques
  • Embryo Implantation
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gestational Age
  • Heterochromatin / genetics
  • Heterochromatin / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Male
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / metabolism
  • Promoter Regions, Genetic
  • Terminal Repeat Sequences

Substances

  • Chaf1a protein, mouse
  • Chromatin Assembly Factor-1
  • Heterochromatin
  • Histones