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A historical account of RegulonDB

U N A M. Campus Morelos. A historical account of RegulonDB. “Swiss-Prot 20 years meeting”, Fortaleza Brazil, August 3 rd , 2006 Julio Collado-Vides Center for Genomic Sciences, UNAM, México. Specific interactions map (i,j) dependency relationships.

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A historical account of RegulonDB

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  1. U N A M Campus Morelos A historical account of RegulonDB “Swiss-Prot 20 years meeting”, Fortaleza Brazil, August 3rd, 2006 Julio Collado-Vides Center for Genomic Sciences, UNAM, México

  2. Specific interactions map (i,j) dependency relationships S1, S2, S3, Sn… T1, T2, T3…Tn

  3. Long distance dependencies: (i,j)works, (i, m) does not work, (k, m) works Collado-Vides (1991) Comput. Applic. Biosci.

  4. Collado-Vides J., Magasanik B. and Gralla J.D. (1991) "Control site location and transcriptional regulation in Escherichia coli" Microbiol. Reviews. 55:371-394

  5. The collection of sigma 54 promoters

  6. Universals of regulation or stamp collection?

  7. A final derivation for a transcription unit • Collado-Vides J. (1992) "Grammatical model of the regulation of gene expression" Proc.Natl.Acad.Sci.USA 89:9405-9409

  8. Predictions. A Linear set of combinations Rosenblueth D.A., Thieffry D., Huerta A.M., Salgado H., and Collado-Vides J. (1996) "Syntactic recognition of regulatory regions in Escherichia coli" CABIOS   12: 415-422.

  9. Map of the complete E.coli sequence.

  10. 90 80 All 70 Activator Repressor 60 Dual Unknown 50 40 30 20 10 0 0 0-10 10 20 20-30 30-40 40-50 50-60 60-70 70-80 80-90 90-100 100-101 HTH Position and Function of Regulators Pérez-Rueda E., and Collado-Vides J. (2000) " Nucleic Acids Research28: 1838-1847

  11. Prediction of operons Distances: between genes inside operons between transcription units

  12. Prediction of operons Salgado et al., (2000) Proc.Natl.Acad.Sci.USA97: 6652-6657

  13. Prediction of operons Moreno-Hagelsieb (2001) Trends in Genetics)

  14. Promoter prediction. Dense Regions of Promoter-like Signals • Huerta A.M. and Collado-Vides J. (2003) Transcription in Dense Regions of Promoter-like SignalsJ.Mol.Biol. 333:261-278

  15. Annotation (Regulation, operon organization) http://www.ccg.unam.mx/Computational_Genomics/regulondb/ http://www.ecocyc.org/

  16. 1. There is a total of 322 transcriptional DNA-binding regulators, from which 183 have experimental evidence and the rest have been predicted based on their helix-turn-helix DNA binding motif. 2. Only MedLine References. 3. Only de active conformations. 4. RegulonDB Relase 5.1 Summary of RegulonDB information by year.

  17. Summary of RegulonDB information by year.

  18. TRN and the Global and Local TFs Martínez-Antonio A. Current Opinion in Microbiology, 2003

  19. Classifying Tfs based on their signal metabolite • TFs were classified on the basis of the cellular location of the signal sensed: • (a) External sensing - signals are localized outside the periplasm, • two-components systems (E-TC) and those using metabolites transported into the cell (E-TM). • (b) Internal sensing: f the signal is inside the periplasmic region (synthesized by the cell or redox) • - synthesized by the cell or redox state (I-SM) • - DNA-bending (I-DB). • (c) Hybrid TFs: The signal is synthesized in the cell, and can be also transported into the cell

  20. Internal sensing regulators govern regulation of regulators • (a) Venn diagram showing the overlap in the transcriptional regulation of regulated genes affected by Internal (32 TFs, 27%), External (62 TFs, 52%) and Hybrid (26TFs, 22%) classes. • (d) Regulation of regulators. Continuous lines -regulation, Dashed lines autoregulation.

  21. Magallanes Project (with Enrique Morett at IBT): Global Transcription Initiation Mapping and Active Promoter Annotation Transcriptional units database Microarray database Primer design Experimental mapping procedure: 5’ RACE (rapid amplification cDNA ends) modificated for high-throughput Active annotation in Regulon DB *Transcription start site *Promoter assignation *Sigma factor assignation Results and data analysis First genomic project of global transcriptional mapping start site for a prokariotic organisms

  22. b0119 (yeaL) Genomic sequence AACGACACAATGCCCGGTGAATGAGATTCCCGGGCATTTTTTTATTTCTAAACCATCGCCGTTCCGCTGTTTTTCTCCG GTAAGGCTGCGATAATTACATCAATGGCGCAATGCGATTTCGGTGCATTGCCGGGAGCAGAGGAACACACTATGGATTA -35 P1 s70 -10 +1 b0391 (yaiE) Genomic sequence TACTGCAAAAACAGCTCGATGTTCCTGTCTTGCTGTCTAACGTATTGATTGCACGGCTGGCTGCGGAATTACTGGTGTA ATTTTGCGTGACAGCCAGCGCCTCTGGCCCCTATAGTGAAGTAGATGTTCAACTACCAAACAGGGCCAGTTTATGCTTC P1 s70 Data up to date -35 -10 +1 Transcriptional units experimentally explored: 421 Transcriptional units experimentally resolved: 164 (145 new data) Experimental growth conditions tested: 3 Magallanes Project. Examples: Hypothetical genes.

  23. Computational Genomics Group Araceli Huerta Ernesto Pérez Rueda David Rosenblueth Denis Thieffry Gabriel Moreno Enrique Morett

  24. The Lord of The Rings: Lessons for Genomics and Bioinformatics Achievement of communities of diversity of beings Ambitious projects

  25. GETools

  26. GETools

  27. Full genome prediction of regulatory binding sites

  28. Full genome prediction of regulatory binding sites

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