Basal gene expression predicts HIF-1 binding. (a) Proportional Venn diagram of genes with MAS5 present calls under normoxic conditions. Genes with basal mRNA production are largely overlapping among U87, HepG2, and MDA-MB231 cells (left panel). For the minority genes that were uniquely present in one cell line but not the other two, there was no overlap in their response to the onset of hypoxia (right panel). (b) Our results suggest that the repertoire of genes active in a cell (for example, through lineage specific transcription factors) defines the subset of genes that are permissive for binding and transactivation by stimulus-responsive transcription factors such as HIF-1. In this way, cell-type-specific differences in response to the same stimulus result, at least in part, from differences in basal gene expression profiles. Upon hypoxia, HIF-1 preferentially binds to active (permissive) loci, as indicated by the presence of H3K4 me3, RNA Pol II, or active mRNA production.