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

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.