Fig. 5: Dnmt mutant embryos show widespread transposon upregulation.

a DNA methylation measured by WGBS and fold change of expression of SINE, LINE, ERV1, ERVK, and EVRL retrotransposons in Dnmt1−/− and DKO embryos. Methylation and expression was calculated on RepeatMasker annotations. b Percentage of significantly upregulated copies within each retrotransposon family in Dnmt1−/− embryos. c Boxplots comparing the size of transposon copies upregulated in Dnmt1−/− embryos (up) or not upregulated (not up) for several ERV families. ***p < 0.001 (Wilcoxon test). In the boxplots the line indicates the median, the box limits indicate the upper and lower quartiles and the whiskers extend to 1.5 IQR from the quartiles. IAPEz-int: n = 4835 (not up), n = 2484 (up), p = 0; MMERVK10C-int: n = 3193 (not up), n = 37 (up), p = 1.53e−14; MMERGLN-int: n = 834 (not up), n = 22 (up), p = 2.15e−12; ERVB4_1B-I_MM-int: n = 1347 (not up), n = 21 (up), p = 8.03e−12; MMETn-int: n = 936 (not up), n = 44 (up), p = 3.97e−14. d Fold change of expression of genes located close to upregulated ERVs (genes ERV up, n = 715) compared with all genes, genes located close to all ERVs (genes ERV all) and a random selection of 715 genes located close to ERVs (genes ERV rand). In the boxplots the line indicates the median, the dot indicates the mean, the box limits indicate the upper and lower quartiles and the whiskers extend to 1.5 IQR from the quartiles. ***p < 0.001 (Wilcoxon test). e Percentage of significantly upregulated genes in Dnmt1−/− embryos for genes located close to upregulated ERVs and control genes. f Cyp2b23 expression is induced by an upstream cluster of ERVs, which initiates a long RNA that splices into the exon 2. The figure shows RNA-seq tracks in WT and Dnmt1−/− embryos, along with splice junctions in one replicate of WT and Dnmt1−/− embryo. ERVs annotated by RepeatMasker are displayed in yellow. g RNA-seq tracks in WT and Dnmt1−/− embryos illustrating that the derepression of an intragenic IAPEz element leads to internal initiation of the Capn11 gene on the opposite strand. The RNA-seq signals from the top (above the line) and bottom (below the line) strands are shown. IAPs annotated by RepeatMasker are displayed in yellow.