Fig. 3: Single-cell profiling of H3K4me3 and H3K27me3 reveals chromatin heterogeneity at KMT2A fusion target loci.
From: Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
a, UMAP projection of the H3K4me3 profiles in single leukemia cells resolves sample-specific clusters. b, Same as in a for H3K27me3. A fraction of cells in the 1° ALL-1, 1° MPAL-1 and 1° MPAL-2 samples intermingle in H3K27me3 UMAP space. c, Same as in a for H3K36me3. Leukemia cells do not form tight sample-specific groups according to H3K36me3 profile. d, Scatterplot comparing the 1° MPAL-1 average imputed H3K4me3 scores and normalized dispersion of genes grouped according to KMT2A fusion-binding status (target, missing target or unbound control) and promoter bivalency status in bulk profiling assays. Select genes are highlighted. e, Same as in d for H3K27me3. f, KMT2A fusion targets show elevated H3K4me3 and H3K27me3 dispersion across select leukemia samples. The center line indicates the median, box limits represent the first and third quartiles, and whiskers show all data within 1.5 times the IQR of the lower and upper quartiles; outliers are not shown. P values were computed using a two-sample t test (two sided). For each sample, n values are listed for bivalent controls, bivalent targets and bivalent missing targets: ML-2: n = 2,425, 14, 14; SEM: n = 3,441, 8, 15; RS4;11: n = 2,635, 6, 9; KOPN-8: n = 2,044, 31, 5; 1° ALL-1: n = 1,873, 6, 9; 1° AML-2: n = 2,483, 17, 12; 1° MPAL-1: n = 3,101, 40, 8; 1° MPAL-2: n = 3,018, 15, 7. g. Organizing genes according to the covariance of H3K4me3 imputed gene scores across 1° MPAL-1 cells resolves groups that vary in concert with one another from cell to cell but are anticorrelated with genes in the other group. Selected genes are highlighted for comparison. h, Same as in g for H3K27me3. i, Imputed H3K4me3 gene scores of the highlighted genes from g and h displayed on a UMAP plot of 1° MPAL-1 cells shown as a dark green cluster in a. j, Same as in i for H3K27me3. HOXA9 and TAPT1 are representative of one group of covariant KMT2A fusion target genes, which are divergent from the second group (for example, CPEB2 and MEIS1).
