Whole genome RNA sequencing analysis to measure the effect of Ehmt2 (G9a, Bat8) deficiencies in somite-staged mouse embryos

ABSTRACT: The experiment was designed to interpret transcription changes in embryos that are developmentally delayed due to different genetically induced deficiencies in the Ehmt2 gene encoding the H3K9 methyltransferase EHMT2. The deficiencies included zygotic homozygosity, maternal mutation, and parental (maternal, paternal, and biparental) haploinsufficiencies, and their respective controls. The age of the embryos was between 8.5 and 9.5 dpc to allow collecting somite-stage matched embryos and detect transcriptome changes shortly before the death of homozygous mutant embryos at 10.5 dpc. Analyzing the homozygous mutants in a novel four-way comparison we distinguished differentially expressed genes (DEGs) that are direct effects of the mutation from those that correspond to embryo development. We separated the developmental DEGs that occur regardless of EHMT2 between the 6-and 12-somite stages, and then identified those developmental DEGs that uniquely change in either the normal or the mutant development. Ehmt2 zygotic and maternal mutant embryos display an increased variance, suggesting that EHMT2 is responsible for narrowing the transcriptional noise after gastrulation. Some transposable element classes correlate with genotype, but others correlate with developmental stage. EHMT2 is required for suppressing long noncoding transcripts that initiate in transposable elements predominantly of the ERVK-class. The ERVK promoters of noncanonical imprinted genes in the embryo require EHMT2 for biallelic silencing and DNA methylation. The transcriptome of delayed parental haploinsufficient wild type embryos is normal, consistent with their good survival prospects. Our four-way comparison approach is generally applicable to functional dissection of essential transcriptional regulators during development.

ORGANISM(S): Mus musculus

PROVIDER: GSE156538 | GEO | 2021/11/01

REPOSITORIES: GEO