Fig. 5: ASXL1^MT-specific distal enhancers are positively associated with gene expression of their putative target genes and can serve as a plausible explanation for the increased transcriptional activity in ASXL1^MT CMML.

a Venn diagram showing the co-mapping of chromatin accessibility and H3K27ac to identify ASXL1^MT-specific cis-regulatory elements. b Signal curves and heatmaps showing the co-occurrence of DNA accessibility and H3K27ac in these ASXL1^MT-specific cis-regulatory elements. c Venn diagram and bar graphs demonstrating the identity of these ASXL1^MT-specific cis-regulatory elements (known enhancers, mostly distally located). d Position weight matrices generated from motif discovery show the over-representation of ETS transcription factors (top 5 enriched motifs) in the ASXL1^MT-specific distal enhancers. e Validation of the predicted ETS transcription factor enrichment in the ASXL1^MT-specific distal enhancers using publicly available human transcription factor ChIP-seq data. f Euler diagrams and bar graphs showing the association between the ASXL1^MT-specific distal enhancers and putative target genes within leukemia-specific topologically associating domains. g Bar graphs showing the distribution of the ASXL1^MT-specific distal enhancers by distance on the linear genome from the transcription start site of their putative target genes. h Box and strip plots demonstrating the association between the presence of distal enhancers and increased gene expression among patients with ASXL1^MT CMML (without evidence for a dosage effect of more than one distal enhancer). i Box and strip plots demonstrating the association between proximity of distal enhancer and putative target gene on the linear genome and increased gene expression of the putative target gene among patients with ASXL1^MT CMML. j Bar graphs showing the functional annotation of the putative target genes of the ASXL1^MT-specific distal enhancers including receptor tyrosine kinase, cytokine, and oncogenic MAPK signaling. Data are presented as standard Tukey boxplots (with the box encompassing Q1 to Q3, the median denoted as a central horizontal line in the box, and the whiskers covering the data within ±1.5 IQR in 5h and i).