Fig. 6: MLL-AF4 binding correlates with high-density TF binding.
From: MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia
a ChIP-seq and ATAC-seq heatmaps at MLL-AF4 peaks in SEM cells. b ChIP-seq for RUNX1, MAZ, MLL, AF4 and H3K27ac, and ATAC-seq at ARID1B. Putative enhancers are highlighted. c Mean ChIP-seq signal at expressed promoters over a 6 kb (left) or 80 kb (right) window. Profiles stratified by MLL-AF4 binding status. d Relationship between RUNX1 peak frequency within gene body and gene body length, stratified by MLL-AF4 binding status as in (c). Local regression (LOESS) lines fit are shown, with 95% confidence interval in gray. Correlation (R) calculated by MLL-AF4 binding status. e Density of RUNX1 ChIP-seq peaks over gene bodies, stratified by proportion of MLL-AF4 coverage, n = 1. Midline shows median, with upper and lower hinges showing the 25th and 75th percentile, respectively. Upper and lower hinges extend to the largest and smallest datapoints within 1.5 times the interquartile range of either hinge. f Mean ChIP-seq signal under control (NT) and 48 h MLL-AF4 knockdown conditions, at expressed promoters of genes containing an MLL-AF4 binding domain >50 kb, over a 6 kb (left) or 80 kb (right) window. g Model for the role of MLL-AF4 at enhancers in driving interaction with and transcription of target genes, recruiting a complex of transcription-associated proteins. Dashed lines indicate the network of protein-protein interactions.
