Co-existing TP53 and ARID1A mutations promote aggressive endometrial tumorigenesis
Fig 6
Analysis of ARID1A chromatin interactions in mouse endometrial epithelia in vivo.
a, Diagram of experimental workflow for measuring ARID1A chromatin interactions in vivo. Endometrial epithelial cells are purified from mouse uterus by positive enrichment with labeling and magnetic beads. Purified cells were then subject to CUT&RUN for ARID1A or IgG negative control. b, Correlation of ARID1A binding signal (compared to IgG) in vivo across 2146 genomic regions with significant binding detected (FDR < 0.25) in two independent experiments. c, Genomic annotation of 2146 ARID1A bound genomic regions in vivo. d, ARID1A binding and accessibility profiles at 3842 bound AP-1/bZIP motifs, using the top de novo enriched motif among ARID1A genome-wide binding sites in vivo, TGA(G/C)TCA. e, Heatmap of ARID1A binding and chromatin accessibility signal across 2146 genomic regions with significant ARID1A binding detected, segregated by accessibility. f, Overlap of ARID1A bound regions and accessible chromatin regions. g, Chromatin accessibility quantified at accessible regions with significantly detected ARID1A binding vs. not. Statistic is two-tailed, unpaired Wilcoxon test. h, Significant overlap of genes with ARID1A promoter binding (within 3kb of TSS) and DE genes from ARID1A/PIK3CA mutant endometrial epithelia. i, Enrichment statistics for top 10 (left) GO Biological Process gene sets and (right) Hallmark pathways among 494 human gene orthologs with ARID1A promoter binding in vivo mouse endometrial epithelia. j, Examples of ARID1A chromatin interactions and accessibility (ATAC) at Hallmark p53 pathway genes in vivo. y-axis is log-likelihood ratio of signal compared to background. Bars underneath signal tracks represent significant (FDR < 0.25) and reproducible (n = 2) signal detection i.e. peaks. phyloP track represents sequence conservation across vertebrates.