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. 2022 Jul 22;13:4247. doi: 10.1038/s41467-022-31919-8

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© The Author(s) 2022

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. 6 — a Distribution of Hi-C counts (contact frequency) between SE60 downregulated cis-genes and the SE60 locus (left) (n = 4), blue points/genes are direct targets. Distribution of Hi-C counts of a background set of 100 distance-matched gene sets (right) (n = 400). The dashed line denotes the cutoff for direct target genes in the experimental sample. b Table displaying the number of direct and indirect cis-target genes of SE60 determined by Hi-C. c CancerSEA analysis of the direct target (p-values determined by GSVA followed by Spearman’s FDR corrected rank test). The red line denotes a p-value of 0.05. d Kaplan–Meier plot of RAE1^34,35. The red line denotes patients with high expression of RAE1, significant p-values are denoted in red. e Hi-C contact heatmap showing the interaction between RAE1 and the SE60 locus (red square). The colored gene names correspond to the fold change of significantly affected genes after CRISPR-KO. f Distribution of all Hi-C counts between SE14 downregulated cis-genes and the SE14 locus (left) (n = 90), blue points/genes are direct targets. Distribution of Hi-C counts of a background set of 100 distance-matched control gene sets (right) (n = 9000). The dashed line denotes the cutoff for direct target genes. g Table displaying the number of direct and indirect cis-target genes of SE14 determined by Hi-C. h CancerSEA pathway analysis of the SE14 direct targets (p-values determined by GSVA followed by Spearman’s FDR corrected rank test). The red line denotes the metric for a p-value of 0.05. i Kaplan–Meier plot of the SE14 direct target genes^34,35. Significant p-values are denoted in red. j Hi-C contact heatmap showing the interaction between EPHA2 and the SE14 locus (red arrow). The colored gene names correspond to the fold change of significantly affected genes after CRISPR-KO. Box plots in a and f are centered on the median, with the bounds of the box being the IQR. The minimum and maximum values, after disregarding outliers, are represented by the upper and lower whiskers. Source data are provided as a Source Data file.