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. 2020 Dec 15;40(6):1191–1202. doi: 10.1038/s41388-020-01591-7

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© The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature 2020

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 Survival map representing prognostic impact of genes encoding key chromatin regulators, based on patient’s disease/relapse-free survival and expression levels. EHMT2/G9a expression levels display a negative impact on disease-free survival in colon adenocarcinoma patients (TCGA COAD). The heat map shows the hazard ratios in log10 scale for tested genes. Red/blue frames indicate significant unfavorable/favorable risk in prognostic analyses (p value ≤ 0.05). B Kaplan–Meier disease-free survival analysis of patients presenting high (top 15%, TPM + 1) and low (bottom 85%, TPM + 1) G9a expression levels in primary CRC tumors (TCGA COAD, n = 275, Logrank p = 0.0028: ***). C Immunofluorescence detection of H3K9me2 in human colon adenocarcinoma sections (n = 39 patients) vs. normal colonic mucosa. Mean fluorescence intensity was quantified using ImageJ (p = 0.0007, ***). D Western analysis of H3K9me2 levels in whole-cell lysates from human normal intestine epithelial crypt cells (HIEC) vs. CRC cell lines SW480, HCT116, and HT29. Total histone H3 was used as loading control. E RNA-seq profiling of key chromatin regulators in human colon adenocarcinoma (TCGA COAD, n = 121). Values are expressed as TPM. F Expression of main H3K9me2 regulators in COAD samples displaying “high” (>0.6, n = 16) and “low” (<0.3, n = 16) mRNA expression-based pluripotent stem cell indices (mRNAsi). TPM values were compared between HI and LO mRNAsi groups for each H3K9me2 regulator (***:p ≤ 0.0001; **:p = 0.0009). G Dose-response experiment assessing the impact of G9a (BIX-01294 and UNC0642), EZH2 (UNC1999), and LSD1 (GSK-LSD1) inhibition on HT29 cell growth (n = 4).