Fig. 4: Chromatin interaction profile and expression patterns of the HOXA cluster in T-ALLs.

a T-ALL subtypes with different HOXA gene expression patterns. HOXA13-translocation (HOXA13-T) negative cases are grouped by unsupervised hierarchical clustering based on the HOXA gene expressions. b ChIP-seq tracks of CTCF and H3K27ac and ATAC-seq tracks in T cell, HOXA⁻ Jurkat and HOXA⁺ Loucy T-ALL cells in the genomic region corresponding to the pink bar of Fig. 4c. CTCF motif orientations, 5′TAD and 3′TAD boundaries and HOXA13-T breakpoints are also included. c Top: a Hi-C heatmap shows the average interaction intensity of HOXA⁻ cases in chr7: 25,750,000-28,250,000 (hg19), which includes HOXA gene cluster and its 3′ and 5′ TADs. Middle left: from top to bottom, Hi-C heatmaps show differential interaction intensities between normal T cell vs. HOXA⁻, 3′ HOXA⁺ vs. HOXA⁻ and 5′ HOXA⁺ vs. HOXA⁻ cases using visual 4C plot. Each line represents interactome of a HOXA gene shown on the left. HOXA5 and HOXA6 share one line as they located in the same bin. The main enhancers are highlighted with orange in the 3′ TAD and blue in the 5′ TAD. Middle right: top right of each heatmap represents the averaged interaction intensities of normal T cell, 3′ HOXA⁺ cases and 5′ HOXA⁺ cases, respectively; bottom left of each heatmap represents the differential interaction intensities between each group and HOXA⁻ cases. Bottom: ChIP-seq tracks for CTCF and H3K27ac and ATAC-seq tracks in T cell, HOXA⁻ Jurkat and HOXA⁺ Loucy T-ALL cells. d Schematic illustrations of the associations among 3D-genomic interactions, HOXA cluster expressions, and associated fusion events in 3′ HOXA cases (left) and 5′ HOXA cases (right). e HOXA13 and HOXA7 expression of HOXA-positive samples with MLL-related (n = 32), NUP98-related (n = 6), SET-NUP214 fusions (n = 3), and HOXA13-T (n = 4). Samples are colored according to translocation.