Hu and Gallo BMC Genomics 2010, 11:49 http://www.biomedcentral.com/1471-2164/11/49 Additional file 4: Shows the 84 tissue-type TF-TF interaction networks from the 11 tissue-type groups. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 49-S4.pdf ] Additional file 5: Lists multiple interacting TFs (3 TFs) and their potential functions for the 79 human tissues. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 49-S5.xls ] Additional file 6: Overlap matrix for multiple interacting TFs. The overlap of multiple interacting TFs between the 79 human tissues is depicted in the upper right panel and overlap of function for multiple interacting TFs in the lower left panel. The degree of overlap is indicated by color with red showing the greatest overlap and yellow showing less overlap. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2164-11- 49-S6.pdf ] Acknowledgements The authors would like to thank Dr. Thomas Furlani for critical reading of the manuscript. This work was partially supported by NIH grant AI28304. Author details 1Center for Computational Research, New York State Center of Excellence in Bioinformatics Life Sciences, Department of Biostatistics, Department of Medicine, State University of New York (SUNY), Buffalo, NY 14260, USA. 2Center for Computational Research, New York State Center of Excellence in Bioinformatics Life Sciences, State University of New York (SUNY), Buffalo, NY 14260, USA. Authors’ contributions ZH initiated and designed the study, conceived the analysis procedure, carried out data analysis, and wrote the manuscript. SG helped write Perl scripts to process data. Both authors read and approved the final manuscript. Received: 16 September 2009 Accepted: 19 January 2010 Published: 19 January 2010 References 1. Arnone MI, Davidson EH: The hardwiring of development: organization and function of genomic regulatory systems. Development (Cambridge, England) 1997, 124(10):1851-1864. 2. Odom DT, Dowell RD, Jacobsen ES, Nekludova L, Rolfe PA, Danford TW, Gifford DK, Fraenkel E, Bell GI, Young RA: Core transcriptional regulatory circuitry in human hepatocytes. Molecular systems biology 2006, 2:2006 0017. 3. Metzger S, Halaas JL, Breslow JL, Sladek FM: Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription. The Journal of biological chemistry 1993, 268(22):16831-16838. 4. Costa RH, Grayson DR: Site-directed mutagenesis of hepatocyte nuclear factor (HNF) binding sites in the mouse transthyretin (TTR) promoter reveal synergistic interactions with its enhancer region. Nucleic Acids Res 1991, 19(15):4139-4145. 5. Rada-Iglesias A, Wallerman O, Koch C, Ameur A, Enroth S, Clelland G, Wester K, Wilcox S, Dovey OM, Ellis PD, et al: Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays. Human molecular genetics 2005, 14(22):3435-3447. 6. Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, et al: Control of pancreas and liver gene expression by HNF transcription factors. Science 2004, 303(5662):1378-1381. Page 14 of 15 7. Rubins NE, Friedman JR, Le PP, Zhang L, Brestelli J, Kaestner KH: Transcriptional networks in the liver: hepatocyte nuclear factor 6 function is largely independent of Foxa2. Molecular and cellular biology 2005, 25(16):7069-7077. 8. Harnish DC, Malik S, Karathanasis SK: Activation of apolipoprotein AI gene transcription by the liver-enriched factor HNF-3. The Journal of biological chemistry 1994, 269(45):28220-28226. 9. Hernandez-Munain C, Krangel MS: Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Molecular and cellular biology 1994, 14(1):473-483. 10. John S, Reeves RB, Lin JX, Child R, Leiden JM, Thompson CB, Leonard WJ: Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I (Y), and NF-kappa B family proteins. Molecular and cellular biology 1995, 15(3):1786-1796. 11. Sartorelli V, Webster KA, Kedes L: Muscle-specific expression of the cardiac alpha-actin gene requires MyoD1, CArG-box binding factor, and Sp1. Genes Dev 1990, 4(10):1811-1822. 12. Naidu PS, Ludolph DC, To RQ, Hinterberger TJ, Konieczny SF: Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis. Molecular and cellular biology 1995, 15(5):2707-2718. 13. Moore ML, Wang GL, Belaguli NS, Schwartz RJ, McMillin JB: GATA-4 and serum response factor regulate transcription of the muscle-specific carnitine palmitoyltransferase I beta in rat heart. The Journal of biological chemistry 2001, 276(2):1026-1033. 14. Bailey PJ, Klos JM, Andersson E, Karlen M, Kallstrom M, Ponjavic J, Muhr J, Lenhard B, Sandelin A, Ericson J: A global genomic transcriptional code associated with CNS-expressed genes. Experimental cell research 2006, 312(16):3108-3119. 15. Krivan W, Wasserman WW: A predictive model for regulatory sequences directing liver-specific transcription. Genome Res 2001, 11(9):1559-1566. 16. Chen X, Blanchette M: Prediction of tissue-specific cis-regulatory modules using Bayesian networks and regression trees. BMC bioinformatics 2007, 8(Suppl 10):S2. 17. Wasserman WW, Fickett JW: Identification of regulatory regions which confer muscle-specific gene expression. Journal of molecular biology 1998, 278(1):167-181. 18. Pennacchio LA, Loots GG, Nobrega MA, Ovcharenko I: Predicting tissue- specific enhancers in the human genome. Genome Res 2007, 17(2):201-211. 19. Yu X, Lin J, Zack DJ, Qian J: Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues. Nucleic Acids Res 2006, 34(17):4925-4936. 20. Smith AD, Sumazin P, Xuan Z, Zhang MQ: DNA motifs in human and mouse proximal promoters predict tissue-specific expression. Proc Natl Acad Sci USA 2006, 103(16):6275-6280. 21. Smith AD, Sumazin P, Zhang MQ: Tissue-specific regulatory elements in mammalian promoters. Molecular systems biology 2007, 3:73. 22. Hu Z, Hu B, Collins JF: Prediction of synergistic transcription factors by function conservation. Genome Biol 2007, 8(12):R257. 23. Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, et al: A gene atlas of the mouse and human protein-encoding transcriptomes. Proc Natl Acad Sci USA 2004, 101(16):6062-6067. 24. Farre D, Bellora N, Mularoni L, Messeguer X, Alba MM: Housekeeping genes tend to show reduced upstream sequence conservation. Genome Biol 2007, 8(7):R140. 25. Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, et al: TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 2006, , 34 Database: D108-110. 26. Tuteja G, Jensen ST, White P, Kaestner KH: Cis-regulatory modules in the mammalian liver: composition depends on strength of Foxa2 consensus site. Nucleic Acids Res 2008, 36(12):4149-4157. 27. Parker GA, Picut CA: Liver immunobiology. Toxicol Pathol 2005, 33(1):52-62. 28. Nguyen P, Leray V, Diez M, Serisier S, Le Bloc’h J, Siliart B, Dumon H: Liver lipid metabolism. J Anim Physiol Anim Nutr (Berl) 2008, 92(3):272-283. 29. Hsu SH, Shyu HW, Hsieh-Li HM, Li H: Spz1, a novel bHLH-Zip protein is specifically expressed in testis. Mechanisms of development 2001, 100(2):177-187.