Fig. 5: Chromatin remodelling of Lrig1 GL distal priming.

a–f, ATAC–seq of sorted Lrig1 GL upper-HF cells (Sca-1⁺) at the four timepoints in distal areas (Distal 3–7 mm from wound bed). Venn diagrams of ATAC–seq peaks (logFC > 0.5, P < 0.05). Peaks from distal area (Distal) at 1w pw1, 8w pw1 and 1w pw2 respect to 0w (gained peaks in red) (a) and shared peaks (red) (b). Density plots (c) depict ATAC–seq signals ±1 kb of 1,665 distal memory peaks (up) and heat map of the signal score of individual peaks (down). Snapshots of genomic loci of representative distal memory peaks (d). GO analysis (e) of genes associated with gained peaks at 1w pw1, 8w pw1 and 1w pw2 versus 0w. −log₁₀ of adjusted p-value (AdjP) is represented by colour scale and gene number by dot size. Transcription factor (TF) motifs (f) enriched in the ATAC–seq peaks gained at 8w pw1_Distal versus 0w, based on de novo motif discovery. g–j, ATAC–seq of Lrig1 GL cultured cells from distal memory (Distal 3–7 mm from wound bed) and control regions (Ctrl distance >2 cm from wound) at 8w pw1. Density plots (g) depict ATAC–seq signals ±1 kb of gained peaks (up) and heat map of the signal score of individual peaks (down) in Distal versus Ctrl cells. Venn diagram (h) of genes associated to gained peaks in 8w pw1_Distal in vitro and associated with distal memory peaks in vivo. Random permutation p-value (P) is shown. GO analysis (i) of genes associated with gained peaks Distal versus Ctrl as −log₁₀(AdjP). Dashed line indicates significance. TF motifs (j) enriched in the ATAC–seq peaks gained in 8w pw1_Distal versus 8w pw1_Ctrl, based on de novo motif discovery. k, RNA-seq of cultured Lrig1 GL cells from Distal and Ctrl. GSEA ranking using the differential gene expression. NES, normalized expression score. Motifs with a match score of >0.8 to a known motif are ranked (f and j). ATAC–seq data (a–j) are the integration of two independent experiments, each of them based on two biological replicates.

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