Fig. 4: TOX epigenetically reprograms self-reactive CD8+ T cells.
From: Persistence of self-reactive CD8+ T cells in the CNS requires TOX-dependent chromatin remodeling
104 naive Tox+/+ or Tox−/− P14 cells were adoptively transferred into WT and MOG-GP mice. One day later (day 0), mice were challenged i.c. with 104 PFU rLCMV-GP33. Brain infiltrating P14 cells were FACS sorted and submitted to ATAC-seq 21 days later. a MDS plot of chromatin accessibility from Tox+/+ or Tox−/− VL and AL cells. Similarity of chromatin accessibility is proportional to the distance between samples. b Number of differentially accessible ChARs in Tox+/+ vs. Tox−/− VL and AL cells (Log2 FC ≥1; FDR < 0.05). c Pie charts showing the distribution for common and variably accessible peaks within promoters, exons, introns and intergenic regions in Tox+/+ vs. Tox−/− VL and AL comparisons. Variable peaks: (Log2 FC ≥1; FDR < 0.05). d Heatmap of the normalized peak intensity for ChARs displaying differential accessibility in at least one comparison (Tox+/+ vs. Tox−/− VL) or (Tox+/+ vs. Tox−/− AL) (Log2 FC ≥1; FDR < 0.05). Hierarchical clustering indicates grouping of samples by TOX-dependent ChAR behavior. Key genes proximal to loci with differential accessibility are indicated for each cluster. Each column represents a biological replicate. e ATAC-seq track of Slamf6 locus for Tox+/+ and Tox−/− VL and AL cells. Differentially accessible ChARs (FDR ≤0.05) are highlighted in gray. f ATAC-seq Z-score of significantly differentially accessible ChARs identified in the comparison Tox+/+ vs. Tox−/− AL (FDR < 0.05) at effector and exhaustion-associated regions33. g ATAC-seq track of Klrg1 locus for Tox+/+ and Tox−/− VL and AL cells. Differentially accessible ChARs (FDR < 0.05) are highlighted in gray. h Enrichment of all known TF motifs within each cluster of differentially accessible ChARs as defined in (d). Color depicts the significance of motif enrichment (hypergeometric test) and circle size indicates the fraction of sequence containing a specific motif. All motifs with an enrichment p-value below 10−3 in at least one cluster are shown. Source data are provided as a Source data file.
