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Volume 162, Issue 5

Genome-wide characterization of monomeric transcriptional regulators in Free

Abstract

Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent . Of the >160 transcriptional regulators annotated in , 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor σ, which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.

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© 2016 The Authors
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2016-05-01
2024-04-20
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References

  1. Alam M. S., Garg S. K., Agrawal P. 2009; Studies on structural and functional divergence among seven WhiB proteins of Mycobacterium tuberculosis H37Rv. FEBS J 276:76–93 [View Article][PubMed]
     [Google Scholar]
  2. Burian J., Ramón-García S., Sweet G., Gómez-Velasco A., Av-Gay Y., Thompson C. J. 2012; The mycobacterial transcriptional regulator whiB7 gene links redox homeostasis and intrinsic antibiotic resistance. J Biol Chem 287:299–310 [View Article][PubMed]
     [Google Scholar]
  3. Burian J., Yim G., Hsing M., Axerio-Cilies P., Cherkasov A., Spiegelman G. B., Thompson C. J. 2013; The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV). Nucleic Acids Res 41:10062–10076 [View Article][PubMed]
     [Google Scholar]
  4. Campbell D. R., Chapman K. E., Waldron K. J., Tottey S., Kendall S., Cavallaro G., Andreini C., Hinds J., Stoker N. G., other authors. 2007; Mycobacterial cells have dual nickel-cobalt sensors: sequence relationships and metal sites of metal-responsive repressors are not congruent. J Biol Chem 282:32298–32310 [View Article][PubMed]
     [Google Scholar]
  5. Casonato S., Cervantes Sánchez A., Haruki H., Rengifo González M., Provvedi R., Dainese E., Jaouen T., Gola S., Bini E., other authors. 2012; WhiB5, a transcriptional regulator that contributes to Mycobacterium tuberculosis virulence and reactivation. Infect Immun 80:3132–3144 [View Article][PubMed]
     [Google Scholar]
  6. Chawla M., Parikh P., Saxena A., Munshi M., Mehta M., Mai D., Srivastava A. K., Narasimhulu K. V., Redding K. E., other authors. 2012; Mycobacterium tuberculosis WhiB4 regulates oxidative stress response to modulate survival and dissemination in vivo . Mol Microbiol 85:1148–1165 [View Article][PubMed]
     [Google Scholar]
  7. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S., other authors. 1998; Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544 [View Article][PubMed]
     [Google Scholar]
  8. Florczyk M. A., McCue L. A., Purkayastha A., Currenti E., Wolin M. J., McDonough K. A. 2003; A family of acr-coregulated Mycobacterium tuberculosis genes shares a common DNA motif and requires Rv3133c (dosR or devR) for expression. Infect Immun 71:5332–5343 [View Article][PubMed]
     [Google Scholar]
  9. Furuta E., Yamamoto K., Tatebe D., Watabe K., Kitayama T., Utsumi R. 2005; Targeting protein homodimerization: a novel drug discovery system. FEBS Lett 579:2065–2070 [View Article][PubMed]
     [Google Scholar]
  10. Gangwar S. P., Meena S. R., Saxena A. K. 2014; Comparison of four different crystal forms of the Mycobacterium tuberculosis ESX-1 secreted protein regulator EspR. Acta Crystallogr F Struct Biol Commun 70:433–437 [View Article][PubMed]
     [Google Scholar]
  11. Geiman D. E., Raghunand T. R., Agarwal N., Bishai W. R. 2006; Differential gene expression in response to exposure to antimycobacterial agents and other stress conditions among seven Mycobacterium tuberculosis whiB-like genes. Antimicrob Agents Chemother 50:2836–2841 [View Article][PubMed]
     [Google Scholar]
  12. Gengenbacher M., Kaufmann S. H. 2012; Mycobacterium tuberculosis: success through dormancy. FEMS Microbiol Rev 36:514–532 [View Article][PubMed]
     [Google Scholar]
  13. Gomez J. E., Bishai W. R. 2000; whmD is an essential mycobacterial gene required for proper septation and cell division. Proc Natl Acad Sci U S A 97:8554–8559 [View Article][PubMed]
     [Google Scholar]
  14. Guo M., Feng H., Zhang J., Wang W., Wang Y., Li Y., Gao C., Chen H., Feng Y., He Z. G. 2009; Dissecting transcription regulatory pathways through a new bacterial one-hybrid reporter system. Genome Res 19:1301–1308 [View Article][PubMed]
     [Google Scholar]
  15. He X., Wang S. 2014; DNA consensus sequence motif for binding response regulator PhoP, a virulence regulator of Mycobacterium tuberculosis . Biochemistry 53:8008–8020 [View Article][PubMed]
     [Google Scholar]
  16. Hu Y., Lu P., Wang Y., Ding L., Atkinson S., Chen S. 2009; OmpR positively regulates urease expression to enhance acid survival of Yersinia pseudotuberculosis . Microbiology 155:2522–2531 [View Article][PubMed]
     [Google Scholar]
  17. Hu Y., Morichaud Z., Perumal A. S., Roquet-Baneres F., Brodolin K. 2014; Mycobacterium RbpA cooperates with the stress-response σB subunit of RNA polymerase in promoter DNA unwinding. Nucleic Acids Res 42:10399–10408 [View Article][PubMed]
     [Google Scholar]
  18. Karimova G., Pidoux J., Ullmann A., Ladant D. 1998; A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A 95:5752–5756 [View Article][PubMed]
     [Google Scholar]
  19. Larsson C., Luna B., Ammerman N. C., Maiga M., Agarwal N., Bishai W. R. 2012; Gene expression of Mycobacterium tuberculosis putative transcription factors whiB1-7 in redox environments. PLoS One 7:e37516 [View Article][PubMed]
     [Google Scholar]
  20. Manganelli R., Provedi R., Rodrigue S., Beaucher J., Gaudreau L., Smith I. 2004; σ Factors and global gene regulation in Mycobacterium tuberculosis . J Bacteriol 186:895–902 [View Article][PubMed]
     [Google Scholar]
  21. Menon S., Wang S. 2011; Structure of the response regulator PhoP from Mycobacterium tuberculosis reveals a dimer through the receiver domain. Biochemistry 50:5948–5957 [View Article][PubMed]
     [Google Scholar]
  22. Murakami K. S., Masuda S., Darst S. A. 2002; Structural basis of transcription initiation: RNA polymerase holoenzyme at 4 Å resolution. Science 296:1280–1284 [View Article][PubMed]
     [Google Scholar]
  23. Parish T. 2014; Two-component regulatory systems of Mycobacteria . Microbiol Spectr 2: MGM2-0010-2013 [PubMed]
     [Google Scholar]
  24. Peterson E. J., Reiss D. J., Turkarslan S., Minch K. J., Rustad T., Plaisier C. L., Longabaugh W. J., Sherman D. R., Baliga N. S. 2014; A high-resolution network model for global gene regulation in Mycobacterium tuberculosis . Nucleic Acids Res 42:11291–11303 [View Article][PubMed]
     [Google Scholar]
  25. Raghunand T. R., Bishai W. R. 2006; Mapping essential domains of Mycobacterium smegmatis WhmD: insights into WhiB structure and function. J Bacteriol 188:6966–6976 [View Article][PubMed]
     [Google Scholar]
  26. Sala C., Haouz A., Saul F. A., Miras I., Rosenkrands I., Alzari P. M., Cole S. T. 2009; Genome-wide regulon and crystal structure of BlaI (Rv1846c) from Mycobacterium tuberculosis . Mol Microbiol 71:1102–1116 [View Article][PubMed]
     [Google Scholar]
  27. Shen A., Higgins D. E., Panne D. 2009; Recognition of AT-rich DNA binding sites by the MogR repressor. Structure 17:769–777 [View Article][PubMed]
     [Google Scholar]
  28. Singh A., Mai D., Kumar A., Steyn A. J. 2006; Dissecting virulence pathways of Mycobacterium tuberculosis through protein–protein association. Proc Natl Acad Sci U S A 103:11346–11351 [View Article][PubMed]
     [Google Scholar]
  29. Smith L. J., Stapleton M. R., Fullstone G. J., Crack J. C., Thomson A. J., Le Brun N. E., Hunt D. M., Harvey E., Adinolfi S., other authors. 2010; Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron–sulfur cluster. Biochem J 432:417–427 [View Article][PubMed]
     [Google Scholar]
  30. Steyn A. J., Collins D. M., Hondalus M. K., Jacobs W. R. Jr, Kawakami R. P., Bloom B. R. 2002; Mycobacterium tuberculosis WhiB3 interacts with RpoV to affect host survival but is dispensable for in vivo growth. Proc Natl Acad Sci U S A 99:3147–3152 [View Article][PubMed]
     [Google Scholar]
  31. Tao J., Han J., Wu H., Hu X., Deng J., Fleming J., Maxwell A., Bi L., Mi K. 2013; Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res 41:2370–2381 [View Article][PubMed]
     [Google Scholar]
  32. van Hijum S. A., Medema M. H., Kuipers O. P. 2009; Mechanisms and evolution of control logic in prokaryotic transcriptional regulation. Microbiol Mol Biol Rev 73:481–509 [View Article][PubMed]
     [Google Scholar]
  33. Zhang Y., Hatch K. A., Bacon J., Wernisch L. 2010; An integrated machine learning approach for predicting DosR-regulated genes in Mycobacterium tuberculosis . BMC Syst Biol 4:37 [View Article][PubMed]
     [Google Scholar]
  34. Zhou X., Lou Z., Fu S., Yang A., Shen H., Li Z., Feng Y., Bartlam M., Wang H., Rao Z. 2010; Crystal structure of ArgP from Mycobacterium tuberculosis confirms two distinct conformations of full-length LysR transcriptional regulators and reveals its function in DNA binding and transcriptional regulation. J Mol Biol 396:1012–1024 [View Article][PubMed]
     [Google Scholar]
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Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis
Microbiology 162, 889 (2016); https://doi.org/10.1099/mic.0.000257
/content/journal/micro/10.1099/mic.0.000257
/content/journal/micro/10.1099/mic.0.000257
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