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. 2023 Mar 27;14:1681. doi: 10.1038/s41467-023-37211-7

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© The Author(s) 2023, corrected publication 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a Volcano plot displaying the differentially expressed genes (DEGs) between the tumor cells of BAP1-mutated tumors (26,806 cells) vs. tumor cells of non-BAP1/PBRM1-mutated tumors (31,002 cells) by snRNA-seq data. Statistical evaluation was performed using a two-sided Wilcoxon rank-sum test, applying Bonferroni correction for the resulting P-values. Dots are colored by whether the genes showed significant and consistent fold changes in individual comparisons of each BAP1-mutated tumor vs. non-BAP1/PBRM1-mutated tumors. b Scatter plot showing the positive correlation of chromatin accessibility and transcriptional changes. The log₂(fold change) of the snRNA-seq expression for each gene (mRNA) is plotted against the log₂(fold change) in the relative snATAC-seq peaks (for all the genes or promoter/enhancer peaks with significant fold change in over 50% of the comparisons for individual BAP1-mutated tumor vs. non-BAP1/PBRM1-mutated tumors). The P-value is derived from a two-sided Spearman rank correlation test (P-value = 2.4e−15). Each dot represents a gene-peak pair. Dots are colored by whether the peak overlaps the gene promoter or is a potential enhancer (co-accessible with the promoter peak). c Heatmap showing the pathways associated with the BAP1-associated DEGs with promoter/enhancer accessibility change (represented in b). d Genomic regions near the CES3 gene in BAP1-mutated tumors vs. non-BAP1-mutated tumors. The plots show the normalized accessibility signal by snATAC-seq around these regions in tumor cells of BAP1-mutant tumors (purple), tumor cells of PBRM1-mutant tumors (orange), tumor cells of non-BAP1/PBRM1-mutant tumors (pink). e Western blot showing BAP1 and Actin protein levels in the BAP1-reconstituted and control SKRC-42 cells. Three independent experiments were performed that showed similar results. f Bar plot showing BAP1 and CES3 gene expression in the BAP1-reconstituted and control SKRC-42 cells. g Schematic diagram showing the differential effects of BAP1 mutations on chromatin accessibility. Created with BioRender.com. Source data are provided as a Source data file.