Genomewide analysis of Runx1 occupancy in pro-B cells confirms binding to enhancer regions and colocalization with SpiB/Pu.1 and Ebf1 binding sites. (A) Distribution of Runx1-bound regions in relation to potential Runx1 target genes demonstrates an enrichment of Runx1 occupancy within close proximity to the regulated genes. The nearest peak to genes deregulated in either gain- or loss-of-function expression or to control genes, exhibiting similar expression levels but whose expression remains constant, was determined. Identified peaks were classified based on their relative position to their associated gene as (1) intragenic (between or coincident with gene boundaries); (2) proximal (within 10 kb upstream or downstream); (3) distal (between 10 and 100 kb upstream or downstream); or (4) >100 kb from gene boundaries. (B) Sequence logos corresponding to enriched sequence elements identified by de novo motif analysis of Runx1-binding sites. The frequency of the enriched motif near Runx1 summits (±100 bp) is indicated (n = 500), as is the calculated E-value. (C) The frequency of Runx1 peaks with a summit mapping at the indicated distance from the summits of E2a, Pax5, or Ebf1 peaks or H3K4me marks in pro-B cells6,24 is shown. (D) Snapshot of relevant gene loci demonstrating association of Runx1-bound regions with E2a-binding sites and regions with mono- and trimethylated H3K4 mapped in pro-B cells6 and DNaseI hypersensitive sites mapped in B cells.50 The University of California - Santa Cruz Genome Browser was used to visualize binding patterns. Vertical rectangles mark regions with proposed enhancer (black) or promoter (green) functions.