Skip to main content
. 2020 May 12;35(2):404–416. doi: 10.1038/s41375-020-0856-3

Fig. 6. Chromatin interactions with the posterior HOXA genes correlate with gene expression in primary AML samples and involve loci with enhancer-associated histone acetylation.

Fig. 6

a Chromatin interactions at chromosome 7p from primary AML sample 507202 with the NPM1c mutation and high HOXA gene expression (see Fig. S1A). Heatmap shows the contact matrix for this sample at 10 kbp resolution. Tracks in the lower panel show statistically supported chromatin loops that involve the HOXA gene cluster. b Chromatin interactions for a primary AML sample with t(8;21)/RUNX1-RUNX1T1 and no HOXA gene expression (see Fig. S1A). Panel components are the same as a. c Focused view of HOXA chromatin loops in the RUNX1-RUNX1T1 (top, in blue) and NPM1c (bottom, in purple) primary AML samples, which highlight the differences in chromatin loop structure and the locations of the loop anchors, which were shifted to the posterior HOXA cluster in the NPM1c-positive sample. d Relative read depth in reads per million of Hi-C reads between the HOXA locus and intron 1 of SKAP2 in the primary samples with NPM1c and RUNX1-RUNX1T1 black and blue, respectively. Interacting reads in the sample with RUNX1-RUNX1T1 are localized to HOXA1 in the anterior HOXA cluster, compared with the NPM1c sample where interacting reads where interacting reads map to CBSA7/9 in the posterior HOXA locus. e Enhancer-associated histone H3 lysine 27 acetylation (H3K27ac) at HOXA interacting loci from primary AML samples with and without HOXA gene expression (including the samples shown in a, b). Primary AML samples include patients with NPM1c (purple; N = 2 distinct patients; the first track is AML 507202 from a and MLL rearrangements (t(9;11) and t(11;19)) (green; N = 2 distinct patients) with high HOXA expression, and samples with t(8;21)/RUNX1-RUNX1T1 (N = 2 distinct patients; the first track is AML 275786 from b). Regions highlighted in the dashed boxes interact with the HOXA cluster in the NPM1c-containing primary sample 507202 (loop track, top), and display H3K27ac signal suggesting they may represent functional genomic elements. e High-resolution view of two loop anchor regions in SKAP2 intron 1 and downstream of the SNX10 gene, which possess the enhancer-associated H3K27ac mark in HOXA-expressing AML samples but not in samples with no HOXA expression.