To address the question of how lineage-determining transcription factors bind to genomic regions in a cell-specific manner, we investigated the genome-wide locations of PU.1 and the effects of loss or gain of other transcription factors on the PU.1 binding pattern in macrophages, B cells and different B cell progenitors. In addition, we assessed the impact of loss and gain of PU.1 on the cistrome of the myeloid-restricted transcription factor, C/EBPβ. Our results suggest that cell type-specific cistromes arise from collaborative interactions between small sets of lineage-determining factors that result in enhanced DNA binding, nucleosome remodelling and subsequent deposition of the epigenetic enhancer mark H3K4me1. The association of PU.1 and its collaborating factors at these genomic locations provides access points for the binding of additional transcription factors, which themselves do not appear to significantly contribute to shaping the overall master regulator genomic distribution, or the overall H3K4me1 pattern, but act to confer transcriptional functions to these distal sites.
