We collect 1,772 known TF recognition motifs (position weight matrices) from primarily large-scale databases67,111-116 and measure their enrichment in the enhancers for each enhancer module compared to the union of the 226 enhancer modules (as described in 67 and 9) using a 0.3 conservation-based confidence cutoff69,72. We cluster motifs using a 0.75 correlation cutoff resulting in 300 motif clusters67 and select for each motif cluster the motif with the highest enrichment in any enhancer module for further analysis.