Figure 3. G9a controls non-canonical imprinting at endogenous retrovirus containing promoters.

(A) Allelic ratio of imprinted genes and the corresponding changes between wildtype (BDF1xCAST) and regulator disrupted embryos within the Epiblast (left) and ExE (right) lineage. Heatmap ranked by the allelic ratio change between WT and ΔDnmt1. For ExE, boxes highlight DNA methylation-independent, non-canonical expressed genes (Asterisk indicates previous description in the literature) and lncRNA directed PRC targets. Notably, ExE-specific imprinting is most apparent for a set of paternally-expressed, G9a-GLP controlled loci that only weakly depend on PRCs. Imprinted genes with less than two informative allelic ratio values in any experimental data set are not shown.

(B) Flow diagram outlining changes in the imprinted landscape between Epiblast and ExE for maternally (top) and paternally (bottom) expressed genes.

(C) Genome browser tracks for E6.5 ExE WGBS and RNA-seq data that cover two non-canonical G9a dependent imprinted clusters Jade1 (top) and Slc38a4 (bottom). Boxes highlight G9a-dependent hypomethylated DMRs (Overlapping ERV LTRs are indicated).

(D) Identified ExE DMRs using WT and ΔG9a WGBS data (1kb window, n = 3,691, |delta cutoff| ≥ 20%). Pie chart showing the proportion of hypo- and hypermethylated DMRs (top). Feature enrichment of the identified DMRs over background was calculated for intergenic, genic (±1kb of TSS), and different repeat classes using the Fisher’s exact test (bottom).