Extended Data Fig. 5: Nucleosome-destabilizing motifs underlie chromatin accessibility noise.
From: Thymic epithelial cells amplify epigenetic noise to promote immune tolerance
a,b, Aggregate histograms of p53 occupancy at AIRE-dependent tissue-specific genes (αTSGs) (blue), p53 CUT&RUN peaks (green) or p53-induced target genes (red) in total mTECs from WT mice. c, Motif enrichment of indicated motifs within 500 bp genomic windows (“tiles”) spanning +/−50 kb of αTSGs (blue) or sites of p53 occupancy (CUT&RUN peaks). d,e, Differences in gene expression of indicated genes between neighboring p53-cHyper and p53-WT mTECs overlayed on scATAC-seq UMAP from Fig. 3b. f, MA plot of the differential expression of genes encoding proteins of the intrinsic apoptosis pathway between mature and immature p53-WT mTECs by bulk RNA-seq (n = 3). Red text=pro-apoptotic, green text=pro-survival proteins. g,h, Differences in gene expression of indicated genes between neighboring p53-cHyper and p53-WT mTECs overlayed on scATAC-seq UMAP from Fig. 3b. i, MA plot of the differential expression of genes encoding DNA damage response proteins between mature and immature p53-cHyper mTECs by bulk RNA-seq. Point colors=Benjamini-Hochberg FDR levels. j, Aggregate histogram of out-of-peak (OOP) Tn5 inserts over αTSGs (blue) or Silent genes (orange) in mature mTECs. k,l, Comparison of transcription factor motif enrichment within scATAC-seq fragments from mature mTECs mapping to within-peak (WIP) (k) or out-of-peak (OOP) (l) at indicated regions versus the adenine/thymine content of each motif. Trendlines (red) with two-sided 95% confidence intervals (t-distribution) for the linear regression fit (gray) indicated. m, MA plot of the expression levels of genes encoding known transcription factors (transcripts per million=TPM) versus the fold-change in expression between transitional and immature mTECs. Motif enrichments (-log10 P value) within scATAC-seq fragments from mature mTECs mapping to out-of-peak regions (OOP frags) +/−100 kb of αTSGs are indicated as point colors. Red dotted line=Ins2 expression in mature mTECs (AIREpos mTEChi). n,o, Comparison of transcription factor motif enrichment within scATAC-seq fragments from mature mTECs mapping to out-of-peak (OOP) regions at indicated loci versus the adenine/thymine content of each motif. Trendlines (red) with two-sided 95% confidence intervals (t-distribution) for the linear regression fit (gray) indicated.
