For discriminative training, we used a three-step process to predict potential enhancers, described in Supplementary Info and ref 68. Two alternative discriminative models converged on a set of ~13,000 putative enhancers in K562 cells68. In the second approach, two methodologically distinct unbiased approaches (see ref 40,69 and M.M. Hoffman et al., manuscript in preparation) converged on a concordant set of histone modification and chromatin-accessibility patterns that can be used to segment the genome in each of the Tier 1 and Tier 2 cell lines, although the individual loci in each state in each cell line are different. With the exception of RNA polymerase II and CTCF, the addition of TF data did not substantially alter these patterns. At this stage, we deliberately excluded RNA and methylation assays, reserving these data as a means to validate the segmentations.