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. 2024 Jan 5;31(3):498–512. doi: 10.1038/s41594-023-01181-7

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© The Author(s) 2024

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. 2 — a, Correlation between average eigenvalues per bin in vehicle-treated and decitabine-treated Gar15-13 PDX tumors. b, Top panel: distribution of stable (A to A; B to B) and switching (A to B; B to A) compartments in decitabine-treated Gar15-13 tumors compared to vehicle-treated tumors. Bottom panel: distribution of different types of switching compartments (A to B; B to A) in decitabine-treated tumors compared to vehicle-treated tumors. c, DNA methylation levels at compartment regions that switched their assignment from B to A and from A to B in decitabine-treated (n = 4 biological replicates) and vehicle-treated (n = 4 biological replicates) PDX tumors. Black line indicates median ± s.d. Box plots show median, interquartile range and maximum–minimum DNA methylation. Data were analyzed using the two-sided Z-test. d, Average contact enrichment (saddle plots) between pairs of 50 kb loci arranged by their PC1 eigenvector in vehicle-treated and decitabine-treated tumors. Average data from n = 3 biological replicates shown. The numbers at the center of the heatmaps indicate compartment strength calculated as the log₂ transformed ratio of (A–A + B–B) / (A–B + B–A) using the mean values. e, Saddle plots calculated using the averaged PC1 obtained from vehicle-treated (n = 3 biological replicates) and decitabine-treated (n = 3 biological replicates) tumors. f, Density plot of insulation scores calculated in vehicle-treated and decitabine-treated tumors. g, Number of TADs identified in vehicle-treated and decitabine-treated (n = 3 biological replicates each) PDX tumors. h, Overlap between TAD boundaries identified in vehicle-treated and decitabine-treated tumors. i, Snapshot of region on chromosome 1, showing vehicle-treated and decitabine-treated tumor Hi-C matrixes. Loss of a TAD in decitabine-treated samples is indicated with an arrow, concomitant with decreased insulation at that region. Merged Hi-C data from replicates (n = 3) at 10 kb resolution. Merged CTCF CUT&RUN signal shown below.

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