1. Compound cis-regulatory elements with both boundary and enhancer functions in the human genome Daudi Jjingo 1, Jianrong Wang 1, Andrew B. Conley 1, Victoria V. Lunyak 2,3 and I. King Jordan 1,3 1 School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA 2 Buck Institute for Research on Aging, Novato, CA 94945, USA 3 PanAmerican Bioinformatics Institute, Santa Marta, Magdalena, Colombia Supplementary Figures

2. 10 Fold enrichment B-E A H3K4me1 H3K27Ac H3K36me3 H3K9Ac H3K4me2 H3K4me3 H4K20me1 H3K27me3 Distance in kb 0-10-55 6 12 18 0 6 12 18 0 Fold enrichment B+E Distance in kb B 010-10-55 DNAse fold enrichment P = 4.0e-7 2 4 6 0 8 B-EB+EE-B P = 0.022 Distance in kb DNAse fold enrichment B+E B-E C 5 10 15 0 100-10-55 20 E-B RNA-seq fold enrichment 3 6 9 0 12 B-EB+E P = 0.01 E-B P = 0.01P = 0.002 RNA-seq fold enrichment Distance in kb D 100-10-55 15 30 45 0 60 B+E B-E E-B B+E fold enrichment 4 8 12 0 E-BE 100-10-55 8 17 26 35 B+E fold enrichment E B+E around E-B B+E around enhancers (E) Supplementary Figure 1. Composite regulatory elements and their features in the human genome. Functional genomic profiles of fold enrichments of individual histone modifications around (A) simple B-E elements and (B) composite B+E elements. (C,D) Enrichment profiles and average fold enrichments for DNAse hypersensitive sites and RNA-seq reads in-and-around boundary elements (blue bars). (E) Enrichment profiles and average fold enrichments for B+E elements around solitary enhancers (E-B) in comparison to their profiles around all enhancers (E).

3. Supplementary Figure 2. Composite regulatory elements and the KEGG chemokine signaling pathway. Chemokine signaling pathway genes(yellow) located or having close homologs proximal to B+E elements. B+E genes Not B+E genesTotal Tissue-specific19929923191 None Tissue-specific15716731 Total21437083922 Supplementary Table 1. Association of tissue-specificity with B+E elements. A 2x2 Contingency table for Fishers' exact test of enrichment of tissue-specific genes around B+E elements (P-value=1.24e-06).