Extended Data Fig. 7: Additional analysis of BLISS in mTECs, related to Fig. 4.
From: AIRE relies on Z-DNA to flag gene targets for thymic T cell tolerization
a, Boxplot comparing BLISS signals at Z-DNA ChIP-seq peaks that had low, medium or high Z-DNA ChIP-seq signals in mTECs from Aire-WT mice. Low: <25th percentile (n = 1508); Medium: 25th - 75th percentile (n = 3008); High: > 75th percentile (n = 1506). b, Boxplot comparing Aire-KO BLISS signals at promoters of AIRE-inducible (n = 1563) and expression-matched AIRE-neutral genes in Aire-KO mTECs (n = 1907). AIRE-inducible and AIRE-neutral genes were weakly expressed genes (Aire-KO TPM < 0.35) whose promoter DSB generation was detected by BLISS in mTECs from Aire-KO mice. c, Boxplot comparing the enrichment of Z-DNA motifs (left) at DSB hotspots upregulated by spermidine (n = 97) versus those unaffected by spermidine (n = 78). Analogous plot for CTCF-binding motifs is shown on the right. The number of motifs was normalized according to the length of the DSB hotspots. d, Correlation between genetic variation in CTCF-binding motifs and allelic imbalance in DSB generation. Individual lines indicate DSB hotspots with a stronger CTCF-binding motif match on the B6 allele (red, n = 60) or on the CAST allele (blue, n = 59). e, Analogous plot for (CA)n repeats (n = 38 for B6 and n = 51 for CAST). p-values for panels a-c were calculated using the Wilcoxon rank sum test (two-tailed), and for panels d and e using the Kolmogorov-Smirnov (KS) test (two-tailed).
