Supplementary Figure 5: Genomic distribution of SNVs is largely unaltered in G9acKO SCCs. | Nature Cell Biology

Supplementary Figure 5: Genomic distribution of SNVs is largely unaltered in G9acKO SCCs.

From: Loss of G9a preserves mutation patterns but increases chromatin accessibility, genomic instability and aggressiveness in skin tumours

Supplementary Figure 5: Genomic distribution of SNVs is largely unaltered in G9acKO SCCs.The alternative text for this image may have been generated using AI.

(a) Heatmap showing unsupervised hierarchical clustering of top 1000 expressed genes between WT and G9acKO tumour progenitors. WT, n = 6 independent SCCs; G9acKO, n = 7 independent SCCs. (b, c) Enrichment in SNV densities in genomic regions with high levels of DHS, H3K36me3, H3K9me3 and RepliChip signal (b) or controlling for epidermal ATAC-seq data from WT or G9acKO epidermis (c). Enrichment is adjusted for the shown variables and trinucleotide content in the genomic regions. Data for A > T transversions (the predominant substitution in DMBA/TPA-induced SCCs) or not A > T transversions are shown. Log enrichments are coefficients from negative binomial regression and their 95% CI, shown in base 2. Enrichments are relative to the lowest genomic bin of each feature (bin 0, below-baseline signal, see methods). (d) Mutation rate of Trp53 locus in not altered in G9acKO SCCs after controlling for replication time. Log enrichments are coefficients from negative binomial regression and their 95% CI, shown in base 2. Enrichments are relative to the genomic bin 0 (see below), which therefore has log2 enrichment = 0 by definition. Bin 3 is the entire Trp53 gene plus flanking 1 Mb (+/- 500 kb to each side); bin 2 is the entire Trp53 gene plus flanking 5 Mb, excluding bin 3; bin 1 is the entire Trp53 gene plus flanking 10 Mb, excluding bin 3 and bin 2; bin 0 is the remainder of the mm9 genome, excluding bins 3, 2 and 1. Trp53 exons + 5nt neighbouring exons were excluded from all analyses in this plot. Genome 37 did not have sufficient mutations within the examined area to perform the regression analysis. Log enrichments for b, c and d are coefficients from negative binomial regression and their 95% CI, shown in base 2. Enrichments are relative to the lowest genomic bin of each feature (bin 0, below-baseline signal, see methods), which thus by definition has log enrichment = 0 and is not shown on plots. DHS, DNase hypersensitivity; SCC, squamous cell carcinoma; SNV, single nucleotide variant

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