H3K9 methyltransferase EHMT2/G9a controls ERVK-driven noncanonical imprinted genes

Epigenomics. 2021 Aug;13(16):1299-1314. doi: 10.2217/epi-2021-0168. Epub 2021 Sep 14.

Abstract

Aim: Paternal allele-specific expression of noncanonical imprinted genes in the extraembryonic lineages depends on an H3K27me3-based imprint in the oocyte, which is not a lasting mark. We hypothesized that EHMT2, the main euchromatic H3K9 dimethyltransferase, also has a role in controlling noncanonical imprinting. Methods: We carried out allele-specific total RNA-seq analysis in the ectoplacental cone of somite-matched 8.5 days post coitum embryos using reciprocal mouse crosses. Results: We found that the maternal allele of noncanonical imprinted genes was derepressed from its ERVK promoter in the Ehmt2-/- ectoplacental cone. In Ehmt2-/- embryos, loss of DNA methylation accompanied biallelic derepression of the ERVK promoters. Canonical imprinting and imprinted X chromosome inactivation were generally undisturbed. Conclusion: EHMT2 is essential for repressing the maternal allele in noncanonical imprinting.

Keywords: EHMT2; ERVK promoters; G9a; noncanonical imprinted genes; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • DNA Methylation
  • Female
  • Gene Expression Regulation*
  • Genomic Imprinting*
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Placenta / metabolism
  • Pregnancy
  • Promoter Regions, Genetic
  • Spermatozoa
  • Whole Genome Sequencing

Substances

  • Biomarkers
  • G9a protein, mouse
  • Histone-Lysine N-Methyltransferase