Fig. 5: Trim28+/D9-dependent cancer susceptibility states are distinguished by distinct early-life epigenomes.
a, Heatmap reporting z-score transformed β values of differentially methylated probes in Trim28+/D9-heavy versus Trim28+/D9-light mice. Effect size cutoff = 0.05; P-value cutoff = 0.001 by t-testing the slope estimates. n = 24 male mice (15 Trim28+/D9-heavy, 9 Trim28+/D9-light). b, MA plot of differential DNA methylation levels (slope estimate) in Trim28+/D9-heavy versus Trim28+/D9-light male mice. Dark and light orange dots represent hypermethylated and hypomethylated probes in Trim28+/D9-light mice, respectively (estimate and P-value cutoff = 0.05 by t-testing the slope estimates). White dots are not significant. n = 24 male mice (15 heavy, 9 light). c, Weight at day 10 of Trim28+/D9-light and Trim28+/D9-heavy male mice used for DNA methylation array experiments. n = 24 male mice (15 heavy, 9 light). P value = 0.089 (unpaired two-sample Wilcoxon test). d, Enrichment plot of Trim28+/D9-light hypomethylated probes in Trim28+/D9-light versus Trim28+/D9-heavy male mice in the indicated tissues. FDR cutoff = 0.01 (one-tailed Fisher’s exact test). n = 46 tissues (12 pancreata, 12 lungs, 11 stomachs, 11 intestines). e,f, Scatterplots showing the correlation by genotype between the average level of DNA methylation on the indicated probe sets (Trim28+/D9-light or Trim28+/D9-heavy hypomethylated probes) and fat mass at 16 weeks. Colors indicate the morphs: Trim28+/D9-light (light orange) and Trim28+/D9-heavy mice (dark orange). n = 58 male mice (7 WT, 24 Trim28+/D9, 11 Trp53R270H/+, 16 Trp53R270H/+;Trim28+/D9).
