Figure 4

dnmt1 and uhrf1 loss activates typeI interferon and NF-kB mediated immune response. (A) RNAseq analysis of RNA extracted from uhrf1^−/− and dnmt1^−/− mutant livers. Four quadrants plot of log₂ fold change of uhrf1^−/− and dnmt1^−/− mutant livers calculated on their own WT siblings. The genes that are significant are indicated in red. Genes that are significant (p_adj < 0.05) in uhrf1^−/− and dnmt1^−/−, in yellow the genes significant only in dnmt1^−/− mutants and in blue the one significant only in the uhrf1^−/− mutant livers. (B) Gene Ontology of the upregulated and downregulated genes in each dataset. Significant genes (p_adj < 0.05) for each category in (A), are divided based on log₂ fold change in upregulated (log₂ Fold Change > 0) and downregulated (log₂ Fold Change < 0). In red the GO terms involved in immune pathways and in green GO terms associated to metabolism and liver specific pathways. (C) Bar graph shows the 20 most significant positively induced pathways according identified in IPA. Pathways are ranked ordered based on z-score and it indicates the likelihood of activation based on comparison with a model that assigns random regulation directions. In red, the immune related pathways. (D) IPA analysis of Interferon pathway. The color of the circles represents the expected trend of the genes when the pathways is upregulated (pink for upregulated and green for downregulated), the color inside the circles represents the observed trend of that gene in our RNAseq. (E) IPA analysis of Tnfa pathway. The color of the circles represents the expected trend of the genes when the pathways is upregulated (pink for upregulated and green for downregulated), the color inside the circles represents the observed trend of that gene in our RNAseq. (F) Metaplot of the DNA methylation levels in WT siblings and uhrf1^−/− mutants of the +/– 4 kb region surrounding the Transcription Start Site of the genes involved in Immune response pathways (GP006955) that are upregulated in the uhrf1^−/−(p_adj < 0.05 and log₂FC > 0, top panel) or not differentially expressed (p_adj > 0.05, bottom panel).