Skip to main content

Advertisement

Log in

The DNA-binding domain as a functional indicator: the case of the AraC/XylS family of transcription factors

Genetica Aims and scope Submit manuscript

Abstract

The AraC/XylS family of transcription factors, which include proteins that are involved in the regulation of diverse biological processes, has been of considerable interest recently and has been constantly expanding by means of in silico predictions and experimental analysis. In this work, using a HMM based on the DNA binding domain of 58 experimentally characterized proteins from the AraC/XylS (A/X), 1974 A/X proteins were found in 149 out of 212 bacterial genomes. This domain was used as a template to generate a phylogenetic tree and as a tool to predict the putative regulatory role of the new members of this family based on their proximity to a particular functional cluster in the tree. Based on this approach we assigned a functional regulatory role for 75% of the TFs dataset. Of these, 33.7% regulate genes involved in carbon-source catabolism, 9.6% global metabolism, 8.3% nitrogen metabolism, 2.9% adaptation responses, 8.9% stress responses, and 11.7% virulence. The abundance of TFs involved in the regulation of metabolic processes indicates that bacteria have optimized their regulatory systems to control energy uptake. In contrast, the lower percentage of TFs required for stress, adaptation and virulence regulation reflects the specialization acquired by each subset of TFs associated with those processes. This approach would be useful in assigning regulatory roles to uncharacterized members of other transcriptional factor families and it might facilitate their experimental analysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Abbreviations

A/X:

AraC/XylS transcription factors

TF:

Transcription factor (s)

DBD:

DNA Binding Domain

EMD:

Effector/Multimerization Domain

EHEC:

Enterohemorrhagic E. coli

EPEC:

Enteropathogenic E. coli

UPEC:

Uropathogenic E. coli

HTH:

Helix-turn-helix

M-C:

Carbon sources metabolism

M-N:

Nitrogen sources utilization

M-G:

Metabolism in general

A-R:

Adaptive responses

S:

Stress

V:

Virulence

References

  • Avison MB (2004) Comparative genomics: digging for data. Methods Mol Biol 266:47–69

    PubMed  CAS  Google Scholar 

  • Bairoch A, Apweiler R (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL. Nucleic Acids Res 28:45–48

    Article  PubMed  CAS  Google Scholar 

  • Barbosa TM, Levy SB (2000) Differential expression of over 60 chromosomal genes in Escherichia coli by constituve expression of MarA. J Bacteriol 182:3467–3474

    Article  PubMed  CAS  Google Scholar 

  • Bateman A, Coin L, Durbin R et al (2004) The Pfam Protein Families Database. Nucleic Acids Res 1(Database issue): D138–D141

    Article  CAS  Google Scholar 

  • Blattner FR, Plunkett G 3rd, Bloch CA et al (1997) The complete genome sequence of Escherichia coli K-12. Science 277:1453–1474

    Article  PubMed  CAS  Google Scholar 

  • Brune I, Brinkrolf K, Kalinowski J, Puhler A et al (2005) The individual and common repertoire of DNA-binding transcriptional regulators of Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium diphtheriae and Corynebacterium jeikeium deduced from the complete genome sequences. BMC Genomics 6:86

    Article  PubMed  CAS  Google Scholar 

  • Brunker P, Hils M, Altenbuchner J et al (1998) The mannitol utilization genes of Pseudomonas fluorescens are regulated by an activator: cloning, nucleotide sequence and expression of the mtlR gene. Gene 215:19–27

    Article  PubMed  CAS  Google Scholar 

  • Buell CR, Joardar V, Lindeberg M et al (2003) The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000. Proc Natl Acad Sci USA 100:10181–10196

    Article  PubMed  CAS  Google Scholar 

  • Daubin V, Gouy M, Perriere G (2002) A phylogenomic approach to bacterial phylogeny: evidence of a core of genes sharing a common history. Genome Res 12:1080–1090

    Article  PubMed  CAS  Google Scholar 

  • Egan SM (2002) Growing repertoire of AraC/XylS activators. J Bacteriol 184:5529–5532

    Article  PubMed  CAS  Google Scholar 

  • Eisen JA (1998) Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis. Genome Res 8:163–167

    PubMed  CAS  Google Scholar 

  • Eisen JA, Fraser CM (2003) Phylogenomics: intersection of evolution and genomics. Science 300:1706–1707

    Article  PubMed  CAS  Google Scholar 

  • Eisen JA, Hanawalt PC (1999) A phylogenomic study of DNA repair genes, proteins, and processes. Mutat Res 435:171–213

    PubMed  CAS  Google Scholar 

  • Gadelle D, Filee J, Buhler C et al (2003) Phylogenomics of type II DNA topoisomerases. Bioessays 25:232–242

    Article  PubMed  CAS  Google Scholar 

  • Gallegos MT, Schleif R, Bairoch A et al (1997) Arac/XylS family of transcriptional regulators. Microbiol Mol Biol Rev 61:393–410

    PubMed  CAS  Google Scholar 

  • Gomez-Duarte OG, Kaper JB (1995) A plasmid-encoded regulatory region activates chromosomal eaeA expression in enteropathogenic Escherichia coli. Infect Immun 63:1767–1776

    PubMed  CAS  Google Scholar 

  • Gough J, Karplus K, Hughey R et al (2001) Assignment of homology to genome sequences using a library of hidden Markov models that represent all proteins of known structure. J Mol Biol 313:903–919

    Article  PubMed  CAS  Google Scholar 

  • Griffith KL, Becker SM, Wolf RJ (2005) Characterization of TetD as a transcriptional activator of a subset of genes of the Escherichia coli SoxS/MarA/Rob regulon. Mol Microbiol 56:1103–1117

    Article  PubMed  CAS  Google Scholar 

  • Heinrichs DE, Poole K (1996) PchR, a regulator of ferripyochelin receptor gene (fptA) expression in Pseudomonas aeruginosa, functions both as an activator and as a repressor. J Bacteriol 178:2586–2592

    PubMed  CAS  Google Scholar 

  • Hentschel U, Steinert M, Hacker J (2000) Common molecular mechanism of symbiosis and pathogenesis. Trends Microbiol 8:226–231

    Article  PubMed  CAS  Google Scholar 

  • Kaper JB, Nataro JP, Mobley HLT (2004) Pathogenic Escherichia coli. Nat Revs 2:123–140

    Article  CAS  Google Scholar 

  • Kwon HJ, Bennik MH, Demple B et al (2000) Crystal structure of the Escherichia coli Rob transcription factor in complex with DNA. Nat Struct Biol 7:424–430

    Article  PubMed  CAS  Google Scholar 

  • Lindler LE, Plana GV, Burland V et al (1998) Complete DNA Sequence and Detailed Analysis of the Yersinia pestis KIM5 Plasmid Encoding Murine Toxin and Capsular Antigen. Infect Immun 66:5731–5742

    PubMed  CAS  Google Scholar 

  • Makita Y, Nakao M, Ogasawara N et al (2004) DBTBS: database of transcriptional regulation in Bacillus subtilis and its contribution to comparative genomics. Nucleic Acids Res 32: D75–D77

    Article  PubMed  CAS  Google Scholar 

  • Martin RG, Gillette WK, Rosner JL (2000) The ykgA gene of Escherichia coli. Mol Microbiol 37:978–979

    Article  PubMed  CAS  Google Scholar 

  • Martin RG, Rosner JL (2001) The AraC transcriptional activators. Curr Opin Microbiol 4:132–137

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Bueno M, Molina-Henares AJ, Pareja E et al (2004) BacTregulators: a database of transcriptional regulators in bacteria and archaea. Bioinformatics 20:2787–2791

    Article  PubMed  CAS  Google Scholar 

  • Moreno-Campuzano S, Chandra JS, Perez-Rueda E (2006) Identification and analysis of DNA-binding Transcription Factors in Bacillus subtilis and other Firmicutes- A genomic approach BMC Genomics 7:147

    Google Scholar 

  • Munson GP, Holcomb LG, Scott JR (2001) Novel group of virulence activators within the AraC family that are not restricted to upstream binding sites. Infect Immun 69:186–193

    Article  PubMed  CAS  Google Scholar 

  • Ochman H, Moran NA (2001) Genes lost and genes found: evolution of bacterial pathogenesis and symbiosis. Science 292:1096–1098

    Article  PubMed  CAS  Google Scholar 

  • Perez-Rueda E, Collado-Vides J (2000) The repertoire of DNA-binding transcriptional regulators in Escherichia coli K-12. Nucleic Acids Res 28:1838–1847

    Article  PubMed  CAS  Google Scholar 

  • Perez-Rueda E, Collado-Vides J, Segovia L (2004) Phylogenetic distribution of DNA-binding transcription factors in bacteria and archaea. Comput Biol Chem 28:341–350

    Article  PubMed  CAS  Google Scholar 

  • Pomposiello PJ, Bennik MHJ, Demple B (2001) Genome-wide transcriptional profiling of the Escherichia coli responses to superoxide stress and sodium salicylate. J Bacteriol 183:3890–3902

    Article  PubMed  CAS  Google Scholar 

  • Porter ME, Smith SG, Dorman CJ (1998) Two highly related regulatory proteins, Shigella flexneri VirF and enterotoxigenic Escherichia coli Rns, have common and distinct regulatory properties. FEMS Microbiol Lett 162:303–309

    Article  PubMed  CAS  Google Scholar 

  • Reimmann C, Serino L, Beyeler M et al (1998) Dihydroaeruginoic acid synthetase and pyochelin synthetase, products of the pchEF genes, are induced by extracellular pyochelin in Pseudomonas aeruginosa. Microbiology 144:3135–3148

    Article  PubMed  CAS  Google Scholar 

  • Rhee S, Martin RG, Rosner JL et al (1998) A novel DNA-binding motif in MarA: the first structure for an AraC family transcriptional activator. Proc Natl Acad Sci USA 95:10413–10418

    Article  PubMed  CAS  Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstruction phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  CAS  Google Scholar 

  • Sicheritz-Ponten T, Andersson SG (2001) A phylogenomic approach to microbial evolution. Nucleic Acids Res 29:545–552

    Article  PubMed  CAS  Google Scholar 

  • Singh A, Gupta R, Vishwakarma RA et al (2005) Requirement of the mymA operon for appropriate cell wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs. J Bacteriol 187:4173–4186

    Article  PubMed  CAS  Google Scholar 

  • Singh A, Jain S, Gupta S et al (2003) mymA operon of Mycobacterium tuberculosis: its regulation and importance in the cell envelope. FEMS Microbiol Lett 227:53–63

    Article  PubMed  CAS  Google Scholar 

  • Sonnhammer EL, Eddy SR, Birney E et al (1998) Pfam: multiple sequence alignments and HMM-profiles of protein domains. Nucleic Acids Res 26:320–322

    Article  PubMed  CAS  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F et al (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882

    Article  PubMed  CAS  Google Scholar 

  • Titball RW, Howells AM, Oyston PC et al (1997) Expression of the Yersinia pestis capsular antigen (F1 antigen) on the surface of an aroA mutant of Salmonella typhimurium induces high levels of protection against plague. Infect Immun 65:1926–1930

    PubMed  CAS  Google Scholar 

  • Tobe T, Schoolnik GK, Sohel I et al (1996) Cloning and characterization of bfpTVW, genes required for the transcriptional activation of bfpA in enteropathogenic Escherichia coli. Mol Microbiol 21:963–975

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Chaudhuri RR, Constantinidou C et al (2004) Regulators encoded in the Escherichia coli type III secretion system 2 gene cluster influence expression of genes within the locus for enterocyte effacement in enterohemorrhagic E. coli O157:H7. J Bacteriol 72:7282–7293

    CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank Enrique Merino, Sarath Chandra Janga and Gabriel Moreno-Hagelsieb for helpful discussions and valuable comment, and Dan Drecktrah for reading and correcting the manuscript. This work was supported by grants from the Universidad Nacional Autónoma de México (DGAPA IN201703-3), from the Consejo Nacional de Ciencia y Tecnología (CONACyT 42918Q) and by an International Research Scholar Award (75301-565101) from the Howard Hughes Medical Institute (HHMI) to JLP. JAI was supported by postdoctoral fellowships from the HHMI and CONACyT. This work was partially supported by a grant (ASTF 224-2005) from EMBO to E. P-R.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to J. Antonio Ibarra or Ernesto Pérez-Rueda.

Additional information

J. Antonio Ibarra and Ernesto Pérez-Rueda contributed equally to this work.

Supplementary material is also available at http://www.ibt.unam.mx/~erueda/AraC_XylS_Family.htm

Electronic supplementary material

Below is the link to the electronic supplementary material.

(DOC 107 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ibarra, J.A., Pérez-Rueda, E., Segovia, L. et al. The DNA-binding domain as a functional indicator: the case of the AraC/XylS family of transcription factors. Genetica 133, 65–76 (2008). https://doi.org/10.1007/s10709-007-9185-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10709-007-9185-y

Keywords

Navigation