Epigenetic activity of phosphorylated PHF8 triggers IFN-I response–mediated apoptosis. (A-H) Deep-proteome quantification analysis of the indicated samples; (A) PCA of all quantified proteins of the samples in the proteome data set (A-H, n = 4 biological replicates per group). (B) Unsupervised hierarchical clustering of differentially regulated proteins between the sample groups as heat map. The color code indicates z scored log 2 protein intensities of multiple sample t test (1-way ANOVA, permutation-based FDR <0.05, significant). (C) Significantly enriched GO terms and pathways. Enrichment analysis (Fisher exact test) of differentially regulated proteins in each of the sample groups. Regulated proteins were compared to the unchanged proteome in the data set based on the GO, KEGG, and keyword terms. (D) Network analysis of enriched pathways for proteins significantly upregulated in PHF8 DD cells. The size and color of nodes indicate number of proteins participating in each pathway. The network analysis was performed in Cytoscape version 3.9.1. (E) Scatterplot comparing the quantified log 2 protein intensities in PHF8 AA vs PHF8 DD cells (data obtained by fractionation proteome experiment, n = 8 fractions per sample). Purple dots indicate proteins participating in response to IFN-I (GO term). The marked protein names represent significant regulations (permutation-based FDR, 0.05). (F) Scatterplot comparing the quantified log 2 protein intensities in PHF8 AA vs PHF8 DD cells (data obtained by fractionation proteome experiment, n = 8 fractions per sample). Pink dots indicate proteins related with apoptotic pathways (GO term). The marked protein names represent significant regulations (permutation-based FDR, 0.05). (G) Venn diagram showing the number of shared proteins between pathways in response to IFN-I and apoptosis in PHF8 DD cells (GO term). (H) Box plot representation of selected significantly regulated proteins participating in response to cell-intrinsic immune response and IFN-I (n = 4 biological replicates per group).