The majority of the MLL-ENL target genes are a subset of MLL wild-type targets. (A) A cartoon of the inducible system shows MLL wild-type and MLL-ENL binding at a target gene. MLL-ENL is fused to the ligand-binding domain of the estrogen receptor (not shown). On binding to a synthetic estrogen derivative 4-hydroxy-tamoxifen (4-OHT), MLL-ENL is released and activates its downstream targets by binding to specific genomic regions (top panel). In the absence of 4-hydroxy-tamoxifen (no 4-OHT), MLL-ENL is retained in a complex with heat shock protein (not shown). Only MLL wild-type protein is bound at the target gene locus (bottom panel). (B) MLL binding intensity under 4-OHT and no 4-OHT conditions were plotted for each of 16 644 genes tiled on the array. Dark gray and black dots represent 2513 wild-type MLL-bound genes. Black dots above and below the diagonal line represent MLL-bound genes with increased binding signal under 4-OHT (223 genes) or no 4-OHT (8 genes) conditions, respectively. (C) Venn diagram shows that ∼ 80% (176) of the 223 MLL differentially binding genes overlap with wild-type MLL target genes.