Fig 2. Arid1a promotes clonal expansion and opening of activation-induced enhancers.

(A) Numbers of WT (black) and Arid1a^cKO (green) P14 cells after infection with LCMV-Armstrong. n=8 (d4.5), 8–11 (d8), 4 (d13), 4 (d21), 8 (d50+). (B) CellTrace Violet dilution of WT and Arid1a^cKO P14 cells at 84h p.i. Frequency of cells that divided 7+ times are quantified in the bar graph. (C) Percentage of ATAC-seq peaks lost (2-fold change, FDR<0.05, Benjamini-Hochberg) in Arid1a^cKO relative to WT cells at d3, d5, and d8 p.i. (D, E) ATAC-seq signal coverage of WT and Arid1a^cKO P14 cells at d3, d5, and d8 p.i. using the same cluster designations defined in Figure 1A. (F) H3K27ac CUT&RUN signal coverage centered on ATAC-seq peaks in WT vs. Arid1a^cKO cells. (G-I) WT and Arid1a^cKO effector cells were isolated at d3 p.i. and compared for differentially expressed genes (DEGs) by RNA-sequencing (>2-fold change, adjusted p-value<0.05, Benjamini-Hochberg). Number of DEGs (G), heatmap of biologically relevant DEGs (H), and gene set enrichment analysis (GSEA) (I) between WT and Arid1a^cKO effector cells are shown. All heatmap genes shown have an adjusted p-value < 0.05. (I) Top 8 Hallmark gene sets (adjusted p value < 0.01, 10,000 permutations) are shown. ns, not significant; *p<0.05, **p<0.005.