GSE171206
Diverse epigenetic mechanisms maintain parental imprints within the embryonic and extraembryonic lineages
Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks at single loci or across chromosome scales remains understudied. Here, we systematically disrupted essential epigenetic pathways within polymorphic F1 embryos to examine canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by the H3K9 methyltransferase G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. From our data, we assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways. Overall design: For this study, we disrupted the DNA methyltransferase Dnmt1, the histone 3 lysine 9 (H3K9) methyltransferases G9a and Glp (target genes Ehmt1 and Ehmt2, double KO), as well as the PRC1 and PRC2 complexes individually (target genes: Rnf2 and Eed, respectively) in BDF1xCAST zygotes. Epiblast and ExE samples were collected from 30 knockout embryos on E6.5 and processed for bulk RNA sequencing.