Fig. 1: Chromatin accessibility changes in self-reactive CD8+ T cells.
From: Persistence of self-reactive CD8+ T cells in the CNS requires TOX-dependent chromatin remodeling
104 naive 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 submitted to ATAC-seq 7 and 21 days after i.c. infection. a Experimental scheme. VE and VL (viral infection early and late) correspond to brain infiltrating P14 cells isolated from WT mice (gray) at early (day 7) or late time point (day 21) after i.c. infection. AE and AL (autoimmunity early and late) correspond to brain infiltrating P14 cells isolated from MOG-GP mice (pink) at early (day 7) or late time point (day 21) after i.c. infection. b Multidimensional scaling (MDS) plot of chromatin accessibility from AE, VE, AL, and VL P14 cells. Similarity of chromatin accessibility is proportional to the distance between samples. c Number of differentially accessible ChARs in each different comparison (Log2 FC ≥1; FDR < 0.05). d Pie charts showing the distribution for common and variably accessible peaks within promoters, exons, introns, and intergenic regions in the comparisons (VE vs. AE) and (VL vs. AL). Variable peaks: (Log2 FC ≥1; FDR < 0.05). e Heatmap of the normalized peak intensity for ChARs displaying differential accessibility in at least one of the comparisons (VE vs. AE) or (VL vs. AL) (Log2 FC ≥1; FDR < 0.05). Hierarchical clustering indicates grouping of samples by ChARs behavior during CNS autoimmunity. Key genes proximal to loci with differential accessibility are indicated for each cluster. Each column represents a biological replicate. f ATAC-seq track of Tox locus for VE, VL, AE, and AL. Differentially accessible ChARs (FDR < 0.05) are highlighted in gray. g ATAC-seq tracks of Pdcd1 locus for VE, VL, AE, and AL. Asterisk corresponds to the exhaustion-specific enhancer at −23.8 kb of the TSS. Differentially accessible ChAR (FDR < 0.05) is highlighted in gray. Representative flow cytometry histogram of PD-1 expression in splenic and brain infiltrating P14 cells isolate from WT mice after rLCMV-GP33 i.c. infection (day 21). h ATAC-seq Z-score of significantly differentially accessible ChARs (FDR < 0.05) at exhaustion-associated regions33. i Enrichment of all known transcription factor (TF) motifs within each cluster of differentially accessible ChARs as defined in (e). 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.
