Here we provide evidence that collaborative interactions between PU.1 and small sets of other lineage-determining transcription factors at closely spaced binding sites establish a large proportion of their respective macrophage and B cell-specific cistromes. The spatial distributions and frequencies of the motifs for each of these factors suggest these patterns arise from direct binding of each factor to its cognate DNA motif rather than tethering of one factor to the other. Conversely, the lack of a fixed distance between the motifs, their enrichment within 100 bp of each other and the nucleosome remodelling observed around sites where inducible PU. 1 binds in PUER cells, often in conjunction with C/EBPβ, is consistent with a mechanism in which concurrent binding of these factors enables effective competition with nucleosomes (Miller and Widom, 2003) to define cell type-specific binding patterns.
