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. 2021 Mar 30;12:1979. doi: 10.1038/s41467-021-22139-7

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© The Author(s) 2021

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. 1 — a Hierarchical clustering of PRAD and NEPC based on sample-to-sample correlation of H3K27ac profiles. “DN” (“double-negative”) indicates a LuCaP PDX without AR or NE marker expression (see also Supplementary Fig. 1). b Heatmaps of normalized H3K27ac tag densities at differentially H3K27-acetylated regions (±2 kb from peak center) between NEPC and PRAD. “CREs” signify candidate regulatory elements. c H3K27ac signal near selected prostate-lineage and NEPC genes. Five representative samples from each histology are shown. d Differential expression (NEPC vs. PRAD) of genes with the indicated number of distinct looped H3K27ac peaks (left) or Ne-CREs (right) detected by H3K27ac HiChIP in LuCaP 173.1 (NEPC). Box boundaries correspond to 1st and 3rd quartiles; whiskers extend to a maximum of 1.5x the inter-quartile range. Two-sided Wilcoxon p-value is indicated for comparison of genes with loops to one Ne-CRE or H3K27ac peak versus two or more. e H3K27ac HiChIP loops in LuCaP 173.1 from ASCL1 to Ne-CREs and NEPC-restricted super-enhancers (Ne-SEs). H3K27ac tag density for LuCaP 173.1 is shown in black. f Candidate master transcription factors in NEPC and PRAD based on regulatory clique enrichment (see methods). g Three most significantly enriched nucleotide motifs present in >10% of Ad-CREs or Ne-CREs by de novo motif analysis. Source data are provided as a Source Data file.