Fig. 1: Distinct 3D chromatin architecture in NEPC compared to CRPC tumors.

a,b, APA plots of NEPC-enriched (a) and CRPC-enriched (b) loops in NEPC (LuCaP93, 145.1, 145.2, and NCI-H660) and CRPC samples (LuCaP35CR, 70CR, 77CR, 147). The APA score is annotated within each plot. Scale bars indicate log₂ of observed over expected enrichment. P = 0.026 and P = 0.022, respectively, for NEPC- and CRPC-enriched loop APA scores between NEPC and CRPC samples. P values by one-sided Student’s t test. c, Volcano plot showing genes linked to NEPC-enriched loops that are differentially expressed in NEPC versus CRPC using P < 0.05 (two-sided t test) and log₂(FC) ≥ 1. d, Volcano plot of genes linked to CRPC-enriched loops and are differentially expressed in CRPC versus NEPC using P < 0.05 (two-sided t test) and log₂(FC) ≥ 1. e,f, GO analyses of genes linked to NEPC-enriched (e) and CRPC-enriched (f) loops and are upregulated in NEPC and CRPC, respectively, as defined in c and d. g,h, Hi-C contact maps (5 kb resolution) of the HOXB gene cluster (g) and AR gene region (h) in CRPC (top row) and NEPC (bottom row) models. Gene boxes and 1D ChIP–seq tracks of matched models are aligned at the bottom. Blue arrows in g indicate NEPC-enriched loops at the HOXB1–HOXB9 loci, and black arrows indicate CRPC-enriched loops at the HOXB13 locus. The scale bars indicate ICE-normalized contact frequency. i,j. The bar graphs showing the percentage of NEPC-enriched (i) or CRPC-enriched (j) loop anchors that overlap with previously reported¹¹ NE-enriched CREs (n = 14,985) and Ad-CREs (n = 4,338). The enriched motifs at overlapped anchors are shown on the right. P values by one-sided permutation test (without multiple comparisons) to evaluate the significant differences of the indicated overlap relative to control regions of equal size.