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FootprintDB: Analysis of Plant Cis-Regulatory Elements, Transcription Factors, and Binding Interfaces

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Plant Synthetic Promoters

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1482))

Abstract

FootprintDB is a database and search engine that compiles regulatory sequences from open access libraries of curated DNA cis-elements and motifs, and their associated transcription factors (TFs). It systematically annotates the binding interfaces of the TFs by exploiting protein–DNA complexes deposited in the Protein Data Bank. Each entry in footprintDB is thus a DNA motif linked to the protein sequence of the TF(s) known to recognize it, and in most cases, the set of predicted interface residues involved in specific recognition. This chapter explains step-by-step how to search for DNA motifs and protein sequences in footprintDB and how to focus the search to a particular organism. Two real-world examples are shown where this software was used to analyze transcriptional regulation in plants. Results are described with the aim of guiding users on their interpretation, and special attention is given to the choices users might face when performing similar analyses.

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References

  1. Stormo GD (2000) DNA binding sites: representation and discovery. Bioinformatics 16(1):16–23

    Article  CAS  PubMed  Google Scholar 

  2. Schneider TD, Stephens RM (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18(20):6097–6100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sebastian A, Contreras-Moreira B (2013) The twilight zone of cis element alignments. Nucleic Acids Res 41(3):1438–1449. doi:10.1093/nar/gks1301

    Article  CAS  PubMed  Google Scholar 

  4. Galas DJ, Schmitz A (1978) DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res 5(9):3157–3170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Garner MM, Revzin A (1981) A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res 9(13):3047–3060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. O’Neill LP, Turner BM (1996) Immunoprecipitation of chromatin. Methods Enzymol 274:189–197

    Article  PubMed  Google Scholar 

  7. Ren B, Robert F, Wyrick JJ, Aparicio O, Jennings EG, Simon I, Zeitlinger J, Schreiber J, Hannett N, Kanin E, Volkert TL, Wilson CJ, Bell SP, Young RA (2000) Genome-wide location and function of DNA binding proteins. Science 290(5500):2306–2309. doi:10.1126/science.290.5500.2306

    Article  CAS  PubMed  Google Scholar 

  8. Berger MF, Bulyk ML (2006) Protein binding microarrays (PBMs) for rapid, high-throughput characterization of the sequence specificities of DNA binding proteins. Methods Mol Biol 338:245–260. doi:10.1385/1-59745-097-9:245

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Johnson DS, Mortazavi A, Myers RM, Wold B (2007) Genome-wide mapping of in vivo protein-DNA interactions. Science 316(5830):1497–1502. doi:10.1126/science.1141319

    Article  CAS  PubMed  Google Scholar 

  10. Ogawa N, Biggin MD (2012) High-throughput SELEX determination of DNA sequences bound by transcription factors in vitro. Methods Mol Biol 786:51–63. doi:10.1007/978-1-61779-292-2_3

    Article  CAS  PubMed  Google Scholar 

  11. Machanick P, Bailey TL (2011) MEME-ChIP: motif analysis of large DNA datasets. Bioinformatics 27(12):1696–1697. doi:10.1093/bioinformatics/btr189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Thomas-Chollier M, Herrmann C, Defrance M, Sand O, Thieffry D, van Helden J (2011) RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets. Nucleic Acids Res. doi:10.1093/nar/gkr1104

    Google Scholar 

  13. Hertz GZ, Stormo GD (1999) Identifying DNA and protein patterns with statistically significant alignments of multiple sequences. Bioinformatics 15(7–8):563–577, doi:btc069 [pii]

    Article  CAS  PubMed  Google Scholar 

  14. Bailey TL, Williams N, Misleh C, Li WW (2006) MEME: discovering and analyzing DNA and protein sequence motifs. Nucleic Acids Res 34(Web Server issue):W369–W373, doi:34/suppl_2/W369 [pii]10.1093/nar/gkl198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Frith MC, Fu Y, Yu L, Chen JF, Hansen U, Weng Z (2004) Detection of functional DNA motifs via statistical over-representation. Nucleic Acids Res 32(4):1372–1381. doi:10.1093/nar/gkh299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen QK, Hertz GZ, Stormo GD (1995) MATRIX SEARCH 1.0: a computer program that scans DNA sequences for transcriptional elements using a database of weight matrices. Comput Appl Biosci 11(5):563–566

    CAS  PubMed  Google Scholar 

  17. Mahony S, Auron PE, Benos PV (2007) DNA familial binding profiles made easy: comparison of various motif alignment and clustering strategies. PLoS Comput Biol 3(3), e61. doi:10.1371/journal.pcbi.0030061

    Article  PubMed  PubMed Central  Google Scholar 

  18. Turatsinze JV, Thomas-Chollier M, Defrance M, van Helden J (2008) Using RSAT to scan genome sequences for transcription factor binding sites and cis-regulatory modules. Nat Protoc 3(10):1578–1588. doi:10.1038/nprot.2008.97

    Article  CAS  PubMed  Google Scholar 

  19. Bailey TL, Gribskov M (1998) Combining evidence using p-values: application to sequence homology searches. Bioinformatics 14(1):48–54

    Article  CAS  PubMed  Google Scholar 

  20. Shortle D, DiMaio D, Nathans D (1981) Directed mutagenesis. Ann Rev Genet 15:265–294. doi:10.1146/annurev.ge.15.120181.001405

    Article  CAS  PubMed  Google Scholar 

  21. O’Neill M, Dryden DT, Murray NE (1998) Localization of a protein-DNA interface by random mutagenesis. EMBO J 17(23):7118–7127. doi:10.1093/emboj/17.23.7118

    Article  PubMed  PubMed Central  Google Scholar 

  22. Morozov AV, Havranek JJ, Baker D, Siggia ED (2005) Protein-DNA binding specificity predictions with structural models. Nucleic Acids Res 33(18):5781–5798. doi:10.1093/nar/gki875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Alamanova D, Stegmaier P, Kel A (2010) Creating PWMs of transcription factors using 3D structure-based computation of protein-DNA free binding energies. BMC Bioinformatics 11:225. doi:10.1186/1471-2105-11-225

    Article  PubMed  PubMed Central  Google Scholar 

  24. Contreras-Moreira B, Collado-Vides J (2006) Comparative footprinting of DNA-binding proteins. Bioinformatics 22(14):e74–e80. doi:10.1093/bioinformatics/btl215

    Article  CAS  PubMed  Google Scholar 

  25. Angarica VE, Perez AG, Vasconcelos AT, Collado-Vides J, Contreras-Moreira B (2008) Prediction of TF target sites based on atomistic models of protein-DNA complexes. BMC Bioinformatics 9:436. doi:10.1186/1471-2105-9-436

    Article  PubMed  PubMed Central  Google Scholar 

  26. Contreras-Moreira B (2010) 3D-footprint: a database for the structural analysis of protein-DNA complexes. Nucleic Acids Res 38(Database issue):D91–D97. doi:10.1093/nar/gkp781

    Article  CAS  PubMed  Google Scholar 

  27. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28(1):235–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sebastian A, Contreras-Moreira B (2014) footprintDB: a database of transcription factors with annotated cis elements and binding interfaces. Bioinformatics 30(2):258–265. doi:10.1093/bioinformatics/btt663

    Article  CAS  PubMed  Google Scholar 

  29. Mathelier A, Zhao X, Zhang AW, Parcy F, Worsley-Hunt R, Arenillas DJ, Buchman S, Chen CY, Chou A, Ienasescu H, Lim J, Shyr C, Tan G, Zhou M, Lenhard B, Sandelin A, Wasserman WW (2014) JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles. Nucleic Acids Res 42(Database issue):D142–D147. doi:10.1093/nar/gkt997

    Article  CAS  PubMed  Google Scholar 

  30. Hume MA, Barrera LA, Gisselbrecht SS, Bulyk ML (2015) UniPROBE, update 2015: new tools and content for the online database of protein-binding microarray data on protein-DNA interactions. Nucleic Acids Res 43(Database issue):D117–D122. doi:10.1093/nar/gku1045

    Article  PubMed  Google Scholar 

  31. Jolma A, Yan J, Whitington T, Toivonen J, Nitta Kazuhiro R, Rastas P, Morgunova E, Enge M, Taipale M, Wei G, Palin K, Vaquerizas Juan M, Vincentelli R, Luscombe Nicholas M, Hughes Timothy R, Lemaire P, Ukkonen E, Kivioja T, Taipale J (2013) DNA-binding specificities of human transcription factors. Cell 152(1):327–339

    Article  CAS  PubMed  Google Scholar 

  32. Kulakovskiy IV, Medvedeva YA, Schaefer U, Kasianov AS, Vorontsov IE, Bajic VB, Makeev VJ (2013) HOCOMOCO: a comprehensive collection of human transcription factor binding sites models. Nucleic Acids Res 41(Database issue):D195–D202. doi:10.1093/nar/gks1089

    Article  CAS  PubMed  Google Scholar 

  33. Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muniz-Rascado L, Garcia-Sotelo JS, Weiss V, Solano-Lira H, Martinez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernandez S, Alquicira-Hernandez K, Lopez-Fuentes A, Porron-Sotelo L, Huerta AM, Bonavides-Martinez C, Balderas-Martinez YI, Pannier L, Olvera M, Labastida A, Jimenez-Jacinto V, Vega-Alvarado L, Del Moral-Chavez V, Hernandez-Alvarez A, Morett E, Collado-Vides J (2013) RegulonDB v80: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res 41(Database issue):D203–D213. doi:10.1093/nar/gks1201

    Article  CAS  PubMed  Google Scholar 

  34. Sierro N, Makita Y, de Hoon M, Nakai K (2008) DBTBS: a database of transcriptional regulation in Bacillus subtilis containing upstream intergenic conservation information. Nucleic Acids Res 36(Database issue):D93–D96. doi:10.1093/nar/gkm910

    CAS  PubMed  Google Scholar 

  35. Bülow L, Engelmann S, Schindler M, Hehl R (2009) AthaMap, integrating transcriptional and post-transcriptional data. Nucleic Acids Res 37(Database issue):D983–D986. doi:10.1093/nar/gkn709

    Article  PubMed  Google Scholar 

  36. Franco-Zorrilla JM, Lopez-Vidriero I, Carrasco JL, Godoy M, Vera P, Solano R (2014) DNA-binding specificities of plant transcription factors and their potential to define target genes. Proc Natl Acad Sci U S A 111(6):2367–2372. doi:10.1073/pnas.1316278111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Down TA, Bergman CM, Su J, Hubbard TJ (2007) Large-scale discovery of promoter motifs in Drosophila melanogaster. PLoS Comput Biol 3(1), e7. doi:10.1371/journal.pcbi.0030007

    Article  PubMed  PubMed Central  Google Scholar 

  38. Enuameh MS, Asriyan Y, Richards A, Christensen RG, Hall VL, Kazemian M, Zhu C, Pham H, Cheng Q, Blatti C, Brasefield JA, Basciotta MD, Ou J, McNulty JC, Zhu LJ, Celniker SE, Sinha S, Stormo GD, Brodsky MH, Wolfe SA (2013) Global analysis of Drosophila Cys(2)-His(2) zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. Genome Res 23(6):928–940. doi:10.1101/gr.151472.112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Matys V, Kel-Margoulis OV, Fricke E, Liebich I, Land S, Barre-Dirrie A, Reuter I, Chekmenev D, Krull M, Hornischer K, Voss N, Stegmaier P, Lewicki-Potapov B, Saxel H, Kel AE, Wingender E (2006) TRANSFAC and its module TRANSCompel: transcriptional gene regulation in eukaryotes. Nucleic Acids Res 34(Database issue):D108–D110. doi:10.1093/nar/gkj143

    Article  CAS  PubMed  Google Scholar 

  40. Higo K, Ugawa Y, Iwamoto M, Korenaga T (1999) Plant cis-acting regulatory DNA elements (PLACE) database: 1999. Nucleic Acids Res 27(1):297–300. doi:10.1093/nar/27.1.297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Davuluri RV, Sun H, Palaniswamy SK, Matthews N, Molina C, Kurtz M, Grotewold E (2003) AGRIS: Arabidopsis gene regulatory information server, an information resource of Arabidopsis cis-regulatory elements and transcription factors. BMC Bioinformatics 4:25. doi:10.1186/1471-2105-4-25

    Article  PubMed  PubMed Central  Google Scholar 

  42. Medina-Rivera A, Defrance M, Sand O, Herrmann C, Castro-Mondragon J, Delerce J, Spinelli L, Jaeger S, Blanchet C, Vincens P, Caron C, Staines D, Contreras-Moreira B, Artufel M, Charbonnier L, Hernandez C, Thieffry D, Thomas-Chollier M, van Helden J (2015) RSAT 2015: Regulatory Sequence Analysis Tools. Nucleic Acids Res 43:W50–W56

    Article  PubMed  PubMed Central  Google Scholar 

  43. Bailey TL, Boden M, Buske FA, Frith M, Grant CE, Clementi L, Ren J, Li WW, Noble WS (2009) MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res 37(Web Server issue):W202–W208. doi:10.1093/nar/gkp335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215(3):403–410. doi:10.1006/jmbi.1990.9999

    Article  CAS  PubMed  Google Scholar 

  45. Mahony S, Benos PV (2007) STAMP: a web tool for exploring DNA-binding motif similarities. Nucleic Acids Res 35(Web Server issue):W253–W258

    Article  PubMed  PubMed Central  Google Scholar 

  46. Finn RD, Bateman A, Clements J, Coggill P, Eberhardt RY, Eddy SR, Heger A, Hetherington K, Holm L, Mistry J, Sonnhammer EL, Tate J, Punta M (2014) Pfam: the protein families database. Nucleic Acids Res 42(Database issue):D222–D230. doi:10.1093/nar/gkt1223

    Article  CAS  PubMed  Google Scholar 

  47. Martinez-Garcia JF, Moyano E, Alcocer MJ, Martin C (1998) Two bZIP proteins from Antirrhinum flowers preferentially bind a hybrid C-box/G-box motif and help to define a new sub-family of bZIP transcription factors. Plant J 13(4):489–505

    Article  CAS  PubMed  Google Scholar 

  48. Dubos C, Kelemen Z, Sebastian A, Bülow L, Huep G, Xu W, Grain D, Salsac F, Brousse C, Lepiniec L, Weisshaar B, Contreras-Moreira B, Hehl R (2014) Integrating bioinformatic resources to predict transcription factors interacting with cis-sequences conserved in co-regulated genes. BMC Genomics 15(1):317. doi:10.1186/1471-2164-15-317

    Article  PubMed  PubMed Central  Google Scholar 

  49. Che D, Jensen S, Cai L, Liu JS (2005) BEST: binding-site estimation suite of tools. Bioinformatics 21(12):2909–2911

    Article  CAS  PubMed  Google Scholar 

  50. Serra TS, Figueiredo DD, Cordeiro AM, Almeida DM, Lourenco T, Abreu IA, Sebastian A, Fernandes L, Contreras-Moreira B, Oliveira MM, Saibo NJ (2013) OsRMC, a negative regulator of salt stress response in rice, is regulated by two AP2/ERF transcription factors. Plant Mol Biol 82(4–5):439–455. doi:10.1007/s11103-013-0073-9

    Article  CAS  PubMed  Google Scholar 

  51. Bryne JC, Valen E, Tang MH, Marstrand T, Winther O, da Piedade I, Krogh A, Lenhard B, Sandelin A (2008) JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update. Nucleic Acids Res 36(Database issue):D102–D106. doi:10.1093/nar/gkm955

    CAS  PubMed  Google Scholar 

  52. Wingender E, Karas H, Knuppel R (1997) TRANSFAC database as a bridge between sequence data libraries and biological function. Pac Symp Biocomput:477–485

    Google Scholar 

  53. Chang WC, Lee TY, Huang HD, Huang HY, Pan RL (2008) PlantPAN: plant promoter analysis navigator, for identifying combinatorial cis-regulatory elements with distance constraint in plant gene groups. BMC Genomics 9:561. doi:10.1186/1471-2164-9-561

    Article  PubMed  PubMed Central  Google Scholar 

  54. Paz-Ares J, Regia C (2002) REGIA, an EU project on functional genomics of transcription factors from Arabidopsis thaliana. Comp Funct Genomics 3(2):102–108. doi:10.1002/cfg.146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We would like to thank our colleagues C. Dubos, L Bülow, N. Saibo, T. Serra and J. van Helden for past and current collaborations. This work was funded by grant Euroinvestigación EUI2008-03612 under the framework of the Transnational (Germany, France, Spain) Cooperation within the PLANT-KBBE Initiative.

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Authors and Affiliations

  1. Estación Experimental de Aula Dei-CSIC, Av. Montañana 1.005, Zaragoza, 50059, Spain

    Bruno Contreras-Moreira

  2. Fundación ARAID, Zaragoza, Spain

    Bruno Contreras-Moreira

  3. Evolutionary Biology Group, Adam Mickievicz University, Poznan, Poland

    Alvaro Sebastian

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  1. Bruno Contreras-Moreira
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  2. Alvaro Sebastian
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Correspondence to Bruno Contreras-Moreira .

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  1. Institut für Genetik, Technische Universität Braunschweig, Braunschweig, Germany

    Reinhard Hehl

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Contreras-Moreira, B., Sebastian, A. (2016). FootprintDB: Analysis of Plant Cis-Regulatory Elements, Transcription Factors, and Binding Interfaces. In: Hehl, R. (eds) Plant Synthetic Promoters. Methods in Molecular Biology, vol 1482. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6396-6_17

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  • DOI: https://doi.org/10.1007/978-1-4939-6396-6_17

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6394-2

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