Fig. 7: TET2 deletion in Jurkat cells influences hypermethylation.
From: Acute lymphoblastic leukemia displays a distinct highly methylated genome
a, Hierarchical clustering with Euclidean distance of all patients with ALL, healthy control and cell line samples (n samples as shown in Fig. 1a) based on the 5% most variable CpGs covered by at least 80% of samples (n = 999,470 CpGs). Samples largely separate by lineage and cell lines overall group to primary samples of the same origin. b, Violin plots showing the mean methylation of variable CGIs (n = 9,349 CGIs, defined across all healthy and ALL samples) for each T-ALL cell line and the T-ALL methylation-based subtypes as well as healthy cells for comparison. White dots denote the median, edges denote the IQR and whiskers denote either 1.5 × IQR or minima/maxima (if no point exceeded 1.5 × IQR; minima/maxima are indicated by the violin plot range). c, Heatmap of epigenetic regulators and their expression status (log2-transformed TPM) in Jurkat and DND41. TET2 is significantly upregulated in Jurkat (adjusted P = 6.35 × 10−27), whereas DNMT1, DNMT3B and WT1 are significantly downregulated in comparison to DND41 (adjusted P = 2.79 × 10−48, 3.46 × 10−44 and 7.41 × 10−88, respectively; two-sided Wald test). d, Pair-wise correlation of CpG methylation levels of Jurkat, Jurkat TET2 KO, PEER and DND41 (blue, low density; red, high density). Black lines mark the difference of 0.1 from the diagonal in both directions. No replicates were generated. e, Box plot of methylation differences across commonly covered sliding windows comparing Jurkat WT and TET2 KO split by HMD and PMD (n = 3,658,861 and 4,855,565 windows, respectively; properties are as in Fig. 2a, covered by all samples considered). Lines denote the median, edges denote the IQR and whiskers denote either 1.5 × IQR or minima/maxima (if no point exceeded 1.5 × IQR; outliers were omitted). TET2 deletion leads to a gain of methylation in both HMDs and PMDs, which is reaching similar levels compared to DND41 in HMDs, whereas PMDs still remain lower. f, Distribution of methylation of 1-kb tiles in HMDs and PMDs (n = 919,527 and 1,216,886 tiles, respectively) as well as variable CGIs (n = 8,863 CGIs) for Jurkat samples with and without TET2 KO as well as compared to DND41 and PEER as control, highly methylated cell lines.
