Extended Data Fig. 9: KMT2C loss gave rise to DNA hypomethylation in SCLC.
(a) The density plot showing all C sites’ methylation levels in the genome of the PRM and PRMK SCLC cells. (b) The 5mC levels of the CpG regions in the PRM and PRMK cells. (c) The density plot showing all C sites’ methylation levels in the genome of the PRM and PRM-Met SCLC cells. (d) The density plot showing the methylation levels of the CpG regions in the CCLE primary and metastasis SCLC cells. (e) The density plot showing the methylation levels of the CpG regions in the CCLE SCLC cells with or without KMT2C mutations. (f) The scatter plot showing the differentially methylated regions (DMRs) in the PRM and PRMK SCLC cells. (g) The scatter plot showing the differentially methylated sites (DMS) in the KMT2C-WT and KMT2C-Mut CCLE SCLC samples. (h) Pie charts showed the genomics region annotation (top) and CpGs subtypes (bottom) of hyper- and hypo- DMRs in PRMK compared to PRM. (i) The Venn diagram showed overlapping of the hypomethylated genes and open genes in PRMK compared to PRM (left); p-value was calculated by a hypergeometric test. The box plot displayed the normalized expression levels of 171 overlap genes of hypomethylated genes and open genes in PRM and PRMK (right), The box bounds the interquartile range divided by the median, with the whiskers extending to a maximum of 1.5 times the interquartile range beyond the box. p-value was calculated by Wilcoxon signed-rank test. (j) Dot blotting showed the expression of 5mC in PRMK organoids with vector or DNMT3A overexpression (left). The statistics of DNA 5mC levels in PRMK cells (right). (mean ± SEM, n = 3). Calculated by Student’s t-test, two-sided. All p-value, *, p < 0.05.
