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  • Expert Recommendation
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Redefining fundamental concepts of transcription initiation in bacteria

Abstract

Despite enormous progress in understanding the fundamentals of bacterial gene regulation, our knowledge remains limited when compared with the number of bacterial genomes and regulatory systems to be discovered. Derived from a small number of initial studies, classic definitions for concepts of gene regulation have evolved as the number of characterized promoters has increased. Together with discoveries made using new technologies, this knowledge has led to revised generalizations and principles. In this Expert Recommendation, we suggest precise, updated definitions that support a logical, consistent conceptual framework of bacterial gene regulation, focusing on transcription initiation. The resulting concepts can be formalized by ontologies for computational modelling, laying the foundation for improved bioinformatics tools, knowledge-based resources and scientific communication. Thus, this work will help researchers construct better predictive models, with different formalisms, that will be useful in engineering, synthetic biology, microbiology and genetics.

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Fig. 1: Schematics of bacterial transcription initiation.
Fig. 2: Eσ intrinsic recognition by a sequence is neither necessary nor sufficient for that sequence to be a promoter.
Fig. 3: Different σ factors that start transcription at the same TSS define different promoters.
Fig. 4: Number of transcription factor binding sites without functional assignment versus number of transcription factor regulatory sites in Escherichia coli.
Fig. 5: Cis-regulatory architecture of the promoter deoCp2.
Fig. 6: Transcription unit and operon schematic.
Fig. 7: Schematic of signal and effector.

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References

  1. Miller, J. H. & Reznikoff, W. S. (eds) The Operon (Cold Spring Harbor Laboratory, 1980).

  2. Beckwith, J. in Escherichia coli and Salmonella: Cellular and Molecular Biology (eds Neidhardt, F. et al.) 1227–1231 (ASM Press, 1996).

  3. Collado-Vides, J., Magasanik, B. & Gralla, J. D. Control site location and transcriptional regulation in Escherichia coli. Microbiol. Rev. 55, 371–394 (1991). This landmark review from the pre-genomics era stresses the importance of promoter architecture rather than sequence.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Galagan, J. E. et al. The Mycobacterium tuberculosis regulatory network and hypoxia. Nature 499, 178–183 (2013). Extensive binding of transcription factors has been found using high-throughput techniques.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Robb, N. C. et al. The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection. J. Mol. Biol. 425, 875–885 (2013).

    CAS  PubMed  Google Scholar 

  6. Eilbeck, K. et al. The Sequence Ontology: a tool for the unification of genome annotations. Genome Biol. 6, R44.1–R44.12 (2005).

    Google Scholar 

  7. Santos-Zavaleta, A. et al. RegulonDB v 10.5: tackling challenges to unify classic and high throughput knowledge of gene regulation in E. coli K-12. Nucleic Acids Res. 47, D212–D220 (2019).

    CAS  PubMed  Google Scholar 

  8. Karp, P. D. et al. The EcoCyc database. EcoSal Plus https://doi.org/10.1128/ecosalplus.ESP-0006-2018 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ruff, E. F., Thomas Record, M. & Artsimovitch, I. Initial events in bacterial transcription initiation. Biomolecules 5, 1035–1062 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Losick, R. & Pero, J. Cascades of sigma factors. Cell 25, 582–584 (1981).

    CAS  PubMed  Google Scholar 

  11. Paget, M. & Helmann, J. Protein family review — the sigma70 family of sigma factors. Genome Biol. 4, 1–6 (2003).

    Google Scholar 

  12. Li, X.-Y. & McClure, W. R. Characterization of the closed complex intermediate formed during transcription initiation by Escherichia coli RNA polymerase. J. Biol. Chem. 273, 23549–23557 (1998).

    CAS  PubMed  Google Scholar 

  13. Saecker, R. M., Record, M. T. & Dehaseth, P. L. Mechanism of bacterial transcription initiation: RNA polymerase–promoter binding, isomerization to initiation-competent open complexes, and initiation of RNA synthesis. J. Mol. Biol. 412, 754–771 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Haugen, S. P., Ross, W. & Gourse, R. L. Advances in bacterial promoter recognition and its control by factors that do not bind DNA. Nat. Rev. Microbiol. 6, 507–519 (2008). This review describes regulators of transcription initiation that do not bind to DNA.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Revyakin, A., Liu, C., Ebright, R. H. & Strick, T. R. Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching. Science 314, 1139–1143 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Greive, S. J. & Von Hippel, P. H. Thinking quantitatively about transcriptional regulation. Nat. Rev. Mol. Cell Biol. 6, 221–232 (2005).

    CAS  PubMed  Google Scholar 

  17. Helmann, J. D. & Pieter, L. Protein–nucleic acid interactions during open complex formation investigated by systematic alteration of the protein and DNA binding partners. Biochemistry 38, 5959–5967 (1999).

    CAS  PubMed  Google Scholar 

  18. Schneider, D. A., Ross, W. & Gourse, R. L. Control of rRNA expression in Escherichia coli. Curr. Opin. Microbiol. 6, 151–156 (2003).

    CAS  PubMed  Google Scholar 

  19. Gourse, R. L. et al. Strength and regulation without transcription factors: lessons from bacterial rRNA promoters. Cold Spring Harb. Symposia Quant. Biol. 63, 131–140 (1998).

    CAS  PubMed  Google Scholar 

  20. Grigorova, I. L., Phleger, N. J., Mutalik, V. K. & Gross, C. A. Insights into transcriptional regulation and σ competition from an equilibrium model of RNA polymerase binding to DNA. Proc. Natl Acad. Sci. USA 103, 5332–5337 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Sorensen, K. I., Baker, K. E., Kelln, R. A. & Neuhard, J. Nucleotide pool-sensitive selection of the transcriptional start site in vivo at the Salmonella typhimurium pyrC and pyrD promoters. J. Bacteriol. 175, 4137–4144 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Turnbough, C. L. Jr. & Switzer, R. L. Regulation of pyrimidine biosynthetic gene expression in bacteria: repression without repressors. Microbiol. Mol. Biol. Rev. 72, 266–300 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Adhya, S., Gottesman, M., Garges, S. & Oppenheim, A. Promoter resurrection by activators — a minireview. Gene 132, 1–6 (1993).

    CAS  PubMed  Google Scholar 

  24. Browning, D. F. & Busby, S. J. W. The regulation of bacterial transcription initiation. Nat. Rev. Microbiol. 2, 1–9 (2004). This review proposes definitions for DNA- and RNAP-centred transcriptional regulators.

    Google Scholar 

  25. Libis, V., Delépine, B. & Faulon, J. L. Sensing new chemicals with bacterial transcription factors. Curr. Opin. Microbiol. 33, 105–112 (2016).

    CAS  PubMed  Google Scholar 

  26. Davidson, E. H. The Regulatory Genome: Gene Regulatory Networks in Development and Evolution (Elsevier, 2010).

  27. Ptashne, M. & Gann, A. Genes & Signals (Cold Spring Laboratory Press, 2002).

  28. Jacob, F., Ullman, A. & Monod, J. Le promoteur, élément génétique nécessaire à l’expression d’un opéron. C. R. Acad. Sci. 258, 3125–3128 (1964). This is the first mention of a bacterial promoter, which is presented almost as a by-product of the operon model.

    CAS  Google Scholar 

  29. Vogt, V. Breaks in DNA stimulate transcription by core RNA polymerase. Nature 223, 854–855 (1969).

    CAS  PubMed  Google Scholar 

  30. Dausse, J. P., Sentenac, A. & Fromageot, P. Interaction of RNA polymerase from Escherichia coli with DNA: influence of DNA scissions on RNA–polymerase binding and chain initiation. Eur. J. Biochem. 31, 394–404 (1972).

    CAS  PubMed  Google Scholar 

  31. Takanami, M., Sugimoto, K., Sugisaki, H. & Okamoto, T. Sequence of promoter for coat protein gene of bacteriophage fd. Nature 260, 297–302 (1976).

    CAS  PubMed  Google Scholar 

  32. Schaller, H., Gray, C. & Herrmann, K. Nucleotide sequence of an RNA polymerase binding site from the DNA of bacteriophage fd. Proc. Natl Acad. Sci. USA 72, 737–741 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Pribnow, D. Nucleotide sequence of an RNA polymerase binding site at an early T7 promoter. Proc. Natl Acad. Sci. USA 72, 784–788 (1975). This first promoter sequence analysis reveals that promoters contain instances of conserved sequence motifs.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ponnambalam, S., Webster, C., Bingham, A. & Busby, S. Transcription initiation at the Escherichia coli galactose operon promoters in the absence of the normal-35 region sequences. J. Biol. Chem. 261, 16043–16048 (1986).

    CAS  PubMed  Google Scholar 

  35. Keilty, S. & Rosenberg, M. Constitutive function of a positively regulated promoter reveals new sequences essential for activity. J. Biol. Chem. 262, 6389–6395 (1987).

    CAS  PubMed  Google Scholar 

  36. Morett, E. & Buck, M. In vivo studies on the interaction of RNA polymerase-σ54 with the Klebsiella pneumoniae and Rhizobium meliloti nifH promoters. J. Mol. Biol. 210, 65–77 (1989).

    CAS  PubMed  Google Scholar 

  37. Travers, A. A. Promoter sequence for stringent control of bacterial ribonucleic acid synthesis. J. Bacteriol. 141, 973–976 (1980). This study highlights the role of the discriminator sequence at bacterial promoters and lays the basis for work on detailed sequence rules.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang, Y. et al. Structural basis of transcription initiation. Science 338, 1076–1080 (2012). Following earlier structures, this publication reveals new details about interactions by the transcription bubble during initiation.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Ross, W. et al. A third recognition element in bacterial promoters: DNA binding by the a subunit of RNA polymerase. Science 262, 1407–1413 (1993). At the culmination of many publications describing the contributions of upstream sequences to promoter activity, this study presents a unified model.

    CAS  PubMed  Google Scholar 

  40. Estrem, S. T. et al. Bacterial promoter architecture: subsite structure of UP elements and interactions with the carboxy-terminal domain of the RNA polymerase a subunit. Genes. Dev. 13, 2134–2147 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Harden, T. T. et al. Bacterial RNA polymerase can retain σ70 throughout transcription. Proc. Natl Acad. Sci. USA 113, 602–607 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Sun, Z. et al. Density of σ70 promoter-like sites in the intergenic regions dictates the redistribution of RNA polymerase during osmotic stress in Escherichia coli. Nucleic Acids Res. 47, 3970–3985 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Huerta, A. M. & Collado-Vides, J. Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals. J. Mol. Biol. 333, 261–278 (2003).

    CAS  PubMed  Google Scholar 

  44. Huerta, A. M., Francino, M. P., Morett, E. & Collado-Vides, J. Selection for unequal densities of σ70 promoter-like signals in different regions of large bacterial genomes. PLoS Genet. 2, 1740–1750 (2006).

    CAS  Google Scholar 

  45. Froula, J. L. & Francino, M. P. Selection against spurious promoter motifs correlates with translational efficiency across bacteria. PLoS One 2, 1–11 (2007).

    Google Scholar 

  46. Yona, A. H., Alm, E. J. & Gore, J. Random sequences rapidly evolve into de novo promoters. Nat. Commun. 9, 1–10 (2018).

    CAS  Google Scholar 

  47. Urtecho, G. et al. Genome-wide functional characterization of Escherichia coli promoters and regulatory elements responsible for their function. Preprint at bioRxiv https://doi.org/10.1101/2020.01.04.894907 (2020).

  48. Jones, B. B., Chan, H., Rothstein, S., Wells, R. D. & Reznikoff, W. S. RNA polymerase binding sites in λplac5 DNA. Proc. Natl Acad. Sci. USA 74, 4914–4918 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Grainger, D. C., Hurd, D., Harrison, M., Holdstock, J. & Busby, S. J. W. Studies of the distribution of Escherichia coli cAMP-receptor protein and RNA polymerase along the E. coli chromosome. Proc. Natl Acad. Sci. USA 102, 17693–17698 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wigneshweraraj, S. et al. Modus operandi of the bacterial RNA polymerase containing the σ54 promoter-specificity factor. Mol. Microbiol. 68, 538–546 (2008).

    CAS  PubMed  Google Scholar 

  51. Bonocora, R. P., Smith, C., Lapierre, P. & Wade, J. T. Genome-scale mapping of Escherichia coli σ54 reveals widespread, conserved intragenic binding. PLoS Genet. 11, 1–30 (2015).

    Google Scholar 

  52. Schaefer, J., Engl, C., Zhang, N., Lawton, E. & Buck, M. Genome wide interactions of wild-type and activator bypass forms of σ54. Nucleic Acids Res. 43, 7280–7291 (2015). This is an authoritative study of the omics of sigma factor 54.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Bono, A. C. et al. Novel DNA binding and regulatory activities for σ54 (RpoN) in Salmonella enterica serovar Thyphimurium 14028s. J. Bacteriol. 199, 1–24 (2017).

    Google Scholar 

  54. Shao, X. et al. RpoN-dependent direct regulation of quorum sensing and the type VI secretion system in Pseudomonas aeruginosa PAO1. J. Bacteriol. 200, 1–17 (2018).

    Google Scholar 

  55. Goldman, S. R., Ebright, R. H. & Nickels, B. E. Direct detection of abortive RNA transcripts in vivo. Science 324, 927–928 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Yus, E. et al. Transcription start site associated RNAs in bacteria. Mol. Syst. Biol. 8, 1–7 (2012).

    Google Scholar 

  57. Dornenburg, J. E., DeVita, A. M., Palumbo, M. J. & Wade, J. T. Widespread antisense transcription in Escherichia coli. MBio 1, 1–4 (2010).

    Google Scholar 

  58. Raghavan, R., Sloan, D. B. & Ochman, H. Pervasive transcription is widespread but rarely conserved in Enteric bacteria. MBio 3, 1–7 (2012).

    Google Scholar 

  59. Sasse-dwight, S. & Gralla, J. A. Y. D. Probing the Escherichia coli glnALG upstream activation mechanism in vivo. Proc. Natl Acad. Sci. USA 85, 8934–8938 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Domínguez-Cuevas, P., Marín, P., Ramos, J. L. & Marqués, S. RNA polymerase holoenzymes can share a single transcription start site for the Pm promoter: critical nucleotides in the –7 to –18 region are needed to select between RNA polymerase with σ38 or σ32. J. Biol. Chem. 280, 41315–41323 (2005).

    PubMed  Google Scholar 

  61. Reichenbach, B., Göpel, Y. & Görke, B. Dual control by perfectly overlapping σ54- and σ70-promoters adjusts small RNA GlmY expression to different environmental signals. Mol. Microbiol. 74, 1054–1070 (2009).

    CAS  PubMed  Google Scholar 

  62. Wade, J. T. et al. Extensive functional overlap between σ factors in Escherichia coli. Nat. Struct. Mol. Biol. 13, 806–814 (2006).

    CAS  PubMed  Google Scholar 

  63. Jacob, F. & Monod, J. Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318–356 (1961).

    CAS  PubMed  Google Scholar 

  64. Pardee, A. B., Jacob, F. & Monod, J. The genetic control and cytoplasmic expression of ‘inducibility’ in the synthesis of β-galactosidase by E. coli. J. Mol. Biol. 1, 165–178 (1959).

    CAS  Google Scholar 

  65. Gilbert, W. & Müller-Hill, B. Isolation of the Lac repressor. Proc. Natl Acad. Sci. USA 56, 1891–1898 (1966). The first characterization of a transcription factor defines these entities as proteins that specifically bind to DNA regions.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Ptashne, M. Specific binding of the λ phage repressor to λ DNA. Nature 214, 232–234 (1967).

    CAS  PubMed  Google Scholar 

  67. Maniatis, T. et al. Recognition sequences of repressor and polymerase in the operators of bacteriophage lambda. Cell 5, 109–113 (1975). This first characterization of a transcription factor binding site describes them as specific regions in the DNA.

    CAS  PubMed  Google Scholar 

  68. Englesberg, E., Irr, J., Power, J. & Lee, N. Positive control of enzyme synthesis by gene C in the L-arabinose system. J. Bacteriol. 90, 946–957 (1965). This landmark paper undermines the belief that regulation must be due to repressors.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Schwartz, M. Aspects biochimiques et génétiques du metabolisme du maltose chez Escherichia coli K12. Comptes Rendus Hebd. Des. Seances De L Acad. Des Sci. 260, 2613 (1965).

    CAS  Google Scholar 

  70. Thomas, R. Control of development in temperate bacteriophages. I. Induction of prophage genes following hetero-immune super-infection. J. Mol. Biol. 22, 79–95 (1966).

    CAS  Google Scholar 

  71. Borukhov, S., Lee, J. & Laptenko, O. Bacterial transcription elongation factors: new insights into molecular mechanism of action. Mol. Microbiol. 55, 1315–1324 (2005).

    CAS  PubMed  Google Scholar 

  72. Storz, G., Opdyke, J. A. & Wassarman, K. M. Regulating bacterial transcription with small RNAs. Cold Spring Harb. Symp. Quant. Biol. 71, 269–273 (2006).

    CAS  PubMed  Google Scholar 

  73. Schwenk, S. & Arnvig, K. B. Regulatory RNA in Mycobacterium tuberculosis, back to basics. Pathog. Dis. 76, 1–12 (2018).

    Google Scholar 

  74. Gourse, R. L. et al. Transcriptional responses to ppGpp and DksA. Annu. Rev. Microbiol. 72, 163–184 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Wassarman, K. M. 6S RNA: a small RNA regulator of transcription. Curr. Opin. Microbiol. 10, 164–168 (2007).

    CAS  PubMed  Google Scholar 

  76. Wassarman, K. M., Repoila, F., Rosenow, C., Storz, G. & Gottesman, S. Identification of novel small RNAs using comparative genomics and microarrays. Genes. Dev. 15, 1637–1651 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Eckweiler, D., Dudek, C.-A., Hartlich, J., Brötje, D. & Jahn, D. PRODORIC2: the bacterial gene regulation database in 2018. Nucleic Acids Res. 46, D320–D326 (2018).

    CAS  PubMed  Google Scholar 

  78. Fornes, O. et al. JASPAR 2020: update of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 48, D87–D92 (2020).

    CAS  PubMed  Google Scholar 

  79. Hu, H. et al. AnimalTFDB 3.0: a comprehensive resource for annotation and prediction of animal transcription factors. Nucleic Acids Res. 47, D33–D38 (2019).

    CAS  PubMed  Google Scholar 

  80. Jin, J. et al. PlantTFDB 4.0: toward a central hub for transcription factors and regulatory interactions in plants. Nucleic Acids Res. 45, D1040–D1045 (2016).

    PubMed  PubMed Central  Google Scholar 

  81. Teixeira, M. C. et al. YEASTRACT: an upgraded database for the analysis of transcription regulatory networks in Saccharomyces cerevisiae. Nucleic Acids Res. 46, D348–D353 (2018).

    CAS  PubMed  Google Scholar 

  82. Paul, B. J. et al. DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell 118, 311–322 (2004).

    CAS  PubMed  Google Scholar 

  83. Gregory, B. D. et al. A regulator that inhibits transcription by targeting an intersubunit interaction of the RNA polymerase holoenzyme. Proc. Natl Acad. Sci. USA 101, 4554–4559 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Pratt, L. A. & Silhavy, T. J. Crl stimulates RpoS activity during stationary phase. Mol. Microbiol. 29, 1225–1236 (1998).

    CAS  PubMed  Google Scholar 

  85. Srivastava, D. B. et al. Structure and function of CarD, an essential mycobacterial transcription factor. Proc. Natl Acad. Sci. USA 110, 12619–12624 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Browning, D. F. & Busby, S. J. W. Local and global regulation of transcription initiation in bacteria. Nat. Rev. Microbiol. 14, 638–650 (2016).

    CAS  PubMed  Google Scholar 

  87. Haldenwang, W. G., Lang, N. & Losick, R. A sporulation-induced sigma-like regulatory protein from B. subtilis. Cell 23, 615–624 (1981).

    CAS  PubMed  Google Scholar 

  88. Grossman, A. D., Erickson, J. W. & Gross, C. A. The htpR gene product of E. coli is a sigma factor for heat-shock promoters. Cell 38, 383–390 (1984).

    CAS  PubMed  Google Scholar 

  89. Taylor, W. E. et al. Transcription from a heat-inducible promoter causes heat shock regulation of the sigma subunit of E. coli RNA polymerase. Cell 38, 371–381 (1984).

    CAS  PubMed  Google Scholar 

  90. Burgess, R. R., Travers, A. A., Dunn, J. J. & Bautz, E. K. Factor stimulating transcription by RNA polymerase. Nature 221, 43–46 (1969).

    CAS  PubMed  Google Scholar 

  91. Feklístov, A., Sharon, B. D., Darst, S. A. & Gross, C. A. Bacterial sigma factors: a historical, structural, and genomic perspective. Annu. Rev. Microbiol. 68, 357–376 (2014). This is a must-read, beautifully written review of bacterial sigma factors, starting with their history.

    PubMed  Google Scholar 

  92. Campagne, S., Marsh, M. E., Capitani, G., Vorholt, J. A. & Allain, F. H. T. Structural basis for –10 promoter element melting by environmentally induced sigma factors. Nat. Struct. Mol. Biol. 21, 269–276 (2014).

    CAS  PubMed  Google Scholar 

  93. Griffith, K. L., Shah, I. M., Myers, T. E., O’Neill, M. C. & Wolf, R. E. Evidence for ‘pre-recruitment’ as a new mechanism of transcription activation in Escherichia coli: The large excess of SoxS binding sites per cell relative to the number of SoxS molecules per cell. Biochem. Biophys. Res. Commun. 291, 979–986 (2002).

    CAS  PubMed  Google Scholar 

  94. Shah, I. M. & Wolf, R. E. Novel protein–protein interaction between Escherichia coli SoxS and the DNA binding determinant of the RNA polymerase α subunit: SoxS functions as a co-sigma factor and redeploys RNA polymerase from UP-element-containing promoters to SoxS-dependent promoters during oxidative stress. J. Mol. Biol. 343, 513–532 (2004).

    CAS  PubMed  Google Scholar 

  95. Li, Z. & Demple, B. Sequence specificity for DNA binding by Escherichia coli SoxS and Rob proteins. Mol. Microbiol. 20, 937–945 (1996).

    CAS  PubMed  Google Scholar 

  96. Kaur, G. et al. Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils. Sci. Rep. 8, 1–13 (2018).

    Google Scholar 

  97. Hubin, E. A. et al. Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA. eLife 6, 1–40 (2017).

    Google Scholar 

  98. Rammohan, J., Manzano, A. R., Garner, A. L., Stallings, C. L. & Galburt, E. A. CarD stabilizes mycobacterial open complexes via a two-tiered kinetic mechanism. Nucleic Acids Res. 43, 3272–3285 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Dorman, C. J., Schumacher, M. A., Bush, M. J., Brennan, R. G. & Buttner, M. J. When is a transcription factor a NAP? Curr. Opin. Microbiol. 55, 26–33 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Schneider, R. et al. An architectural role of the Escherichia coli chromatin protein FIS in organising DNA. Nucleic Acids Res. 29, 5107–5114 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Dillon, S. C. & Dorman, C. J. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat. Rev. Microbiol. 8, 185–195 (2010).

    CAS  PubMed  Google Scholar 

  102. Dame, R. T. The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin. Mol. Microbiol. 56, 858–870 (2005).

    CAS  PubMed  Google Scholar 

  103. Blot, N., Mavathur, R., Geertz, M., Travers, A. & Muskhelishvili, G. Homeostatic regulation of supercoiling sensitivity coordinates transcription of the bacterial genome. EMBO Rep. 7, 710–715 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Rimsky, S., Zuber, F., Buckle, M. & Buc, H. A molecular mechanism for the repression of transcription by the H-NS protein. Mol. Microbiol. 42, 1311–1323 (2001).

    CAS  PubMed  Google Scholar 

  105. Opel, M. L. et al. Activation of transcription initiation from a stable RNA promoter by a Fis protein-mediated DNA structural transmission mechanism. Mol. Microbiol. 53, 665–674 (2004).

    CAS  PubMed  Google Scholar 

  106. Ihara, K. et al. Expression of the alaE gene is positively regulated by the global regulator Lrp in response to intracellular accumulation of L-alanine in Escherichia coli. J. Biosci. Bioeng. 123, 444–450 (2017).

    CAS  PubMed  Google Scholar 

  107. Finkel, S. E. & Johnson, R. C. The Fis protein: it’s not just for DNA inversion anymore. Mol. Microbiol. 7, 1023–1023 (1993).

    CAS  PubMed  Google Scholar 

  108. Brandi, A., Giangrossi, M., Giuliodori, A. M. & Falconi, M. An interplay among FIS, H-NS, and guanosine tetraphosphate modulates transcription of the Escherichia coli cspA gene under physiological growth conditions. Front. Mol. Biosci. 3, 1–12 (2016).

    Google Scholar 

  109. Govantes, F., Orjalo, A. V. & Gunsalus, R. P. Interplay between three global regulatory proteins mediates oxygen regulation of the Escherichia coli cytochrome d oxidase (cydAB) operon. Mol. Microbiol. 38, 1061–1073 (2000).

    CAS  PubMed  Google Scholar 

  110. Meenakshi, S., Karthik, M. & Munavar, M. H. A putative curved DNA region upstream of rcsA in Escherichia coli plays a key role in transcriptional regulation by H-NS. FEBS Open. Bio 8, 1209–1218 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Carmona, M., Claverie-Martin, F. & Magasanik, B. DNA bending and the initiation of transcription at σ54-dependent bacterial promoters. Proc. Natl Acad. Sci. USA 94, 9568–9572 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Ninfa, A. J., Reitzer, L. J. & Magasanik, B. Initiation of transcription at the bacterial glnAp2 promoter by purified E. coli components is facilitated by enhancers. Cell 50, 1039–1046 (1987).

    CAS  PubMed  Google Scholar 

  113. Azam, T. A. & Ishihama, A. Twelve species of the nucleoid-associated protein from Escherichia coli. J. Biol. Chem. 274, 33105–33113 (1999).

    CAS  PubMed  Google Scholar 

  114. Martinez-Antonio, A. & Collado-Vides, J. Identifying global regulators in transcriptional regulatory networks in bacteria. Curr. Opin. Microbiol. 6, 482–489 (2003).

    CAS  PubMed  Google Scholar 

  115. Santos-Zavaleta, A. et al. A unified resource for transcriptional regulation in Escherichia coli K-12 incorporating high-throughput-generated binding data into RegulonDB version 10.0. BMC Biol. 16, 1–12 (2018). This reports on the most recent update of the RegulonDB database on regulation of transcription initiation and operon organization in E. coli.

    Google Scholar 

  116. Galagan, J., Lyubetskaya, A. & Gomes, A. ChIP-Seq and the complexity of bacterial transcriptional regulation. Curr. Top. Microbiol. Immunol. 363, 43–68 (2013).

    CAS  PubMed  Google Scholar 

  117. Babin, B. M. et al. SutA is a bacterial transcription factor expressed during slow growth in Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 113, E597–E605 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Jones, C. J. et al. ChIP-Seq and RNA-Seq reveal an AmrZ-mediated mechanism for cyclic di-GMP synthesis and biofilm development by Pseudomonas aeruginosa. PLoS Pathog. 10, e1003984 (2014).

    PubMed  PubMed Central  Google Scholar 

  119. Perkins, T. T. et al. ChIP-seq and transcriptome analysis of the OmpR regulon of Salmonella enterica serovars Typhi and Typhimurium reveals accessory genes implicated in host colonization. Mol. Microbiol. 87, 526–538 (2013).

    CAS  PubMed  Google Scholar 

  120. Lobel, L. & Herskovits, A. A. Systems level analyses reveal multiple regulatory activities of CodY controlling metabolism, motility and virulence in Listeria monocytogenes. PLoS Genet. 12, 1–27 (2016).

    Google Scholar 

  121. Vannini, A. et al. Comprehensive mapping of the Helicobacter pylori NikR regulon provides new insights in bacterial nickel responses. Sci. Rep. 7, 1–14 (2017).

    Google Scholar 

  122. Vergara-Irigaray, M., Fookes, M. C., Thomson, N. R. & Tang, C. M. RNA-seq analysis of the influence of anaerobiosis and FNR on Shigella flexneri. BMC Genomics 15, 1–22 (2014).

    Google Scholar 

  123. Grainger, D. C. et al. Genomic studies with Escherichia coli MelR protein: applications of chromatin immunoprecipitation and microarrays. J. Bacteriol. 186, 6938–6943 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Sharma, P. et al. The multiple antibiotic resistance operon of enteric bacteria controls DNA repair and outer membrane integrity. Nat. Commun. 8, 1444 (2017).

  125. Visweswariah, S. S. & Busby, S. J. W. Evolution of bacterial transcription factors: how proteins take on new tasks, but do not always stop doing the old ones. Trends Microbiol. 23, 463–467 (2015).

    CAS  PubMed  Google Scholar 

  126. Beauchene, N. A. et al. Impact of anaerobiosis on expression of the iron-responsive Fur and RyhB regulons. MBio 6, e01947-15 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Gao, Y. et al. Systematic discovery of uncharacterized transcription factors in Escherichia coli K-12 MG1655. Nucleic Acids Res. 46, 10682–10696 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Shimada, T., Ishihama, A., Busby, S. J. W. & Grainger, D. C. The Escherichia coli RutR transcription factor binds at targets within genes as well as intergenic regions. Nucleic Acids Res. 36, 3950–3955 (2008). This first genome-wide study shows a large fraction of intergenic TF sites.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Wade, J. T., Reppas, N. B., Church, G. M. & Struhl, K. Genomic analysis of LexA binding reveals the permissive nature of the Escherichia coli genome and identifies unconventional target sites. Genes Dev. 19, 2619–2630 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Myers, K. S. et al. Genome-scale analysis of Escherichia coli FNR reveals complex features of transcription factor binding. PLoS Genet. 9, e1003565 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Kroner, G. M., Wolfe, M. B. & Freddolino, P. L. Escherichia coli Lrp regulates one-third of the genome via direct, cooperative, and indirect routes. J. Bacteriol. 201, e00411–18 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Jacob, F., Perrin, D., Sanchez, C. & Monod, J. L’opéron: groupe de gènes à expression coordonnée par un opérateur. C. R. Acad. Sci. 250, 1727–1729 (1960). This report provides the original definition of an operon as a set of co-transcribed genes whose expression is coordinated by an operator.

    CAS  Google Scholar 

  133. Gralla, J. D. & Collado-Vides, J. in Escherichia coli and Salmonella: Cellular and Molecular Biology (eds Neidhardt, F. & Curtiss, R.) 1232–1245 (ASM Press, 1996).

  134. Collado-Vides, J. et al. Bioinformatics resources for the study of gene regulation in bacteria. J. Bacteriol. 91, 23–31 (2009).

    Google Scholar 

  135. Reitzer, L. J. & Magasanik, B. Transcription of glnA in E. coli is stimulated by activator bound to sites far from the promoter. Cell 45, 785–792 (1986).

    CAS  PubMed  Google Scholar 

  136. Claverie-Martin, F. & Magasanik, B. Role of integration host factor in the regulation of the glnHp2 promoter of Escherichia coli. Proc. Natl Acad. Sci. USA 88, 1631–1635 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Gralla, J. D. Promoter recognition and mRNA initiation by Escherichia coli70. Methods Enzymol. 185, 37–54 (1990).

    CAS  PubMed  Google Scholar 

  138. Hancock, J. M. & Zvelebil, M. J. Concise Encyclopaedia of Bioinformatics and Computational Biology (Wiley, 2014).

  139. Collado-Vides, J. The search for a grammatical theory of regulation is formally justified by showing the inadequacy of context-free grammars. Bioinformatics 7, 321–326 (1991).

    CAS  Google Scholar 

  140. Buchler, N. E., Gerland, U. & Hwa, T. On schemes of combinatorial transcription logic. Proc. Natl Acad. Sci. USA 100, 5136–5141 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Bintu, L. et al. Transcriptional regulation by the numbers: applications. Curr. Opin. Genet. Dev. 15, 125–135 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Phillips, R. et al. Figure 1 theory meets figure 2 experiments in the study of gene expression. Annu. Rev. Biophys. 48, 121–163 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Bintu, L. et al. Transcriptional regulation by the numbers: models. Curr. Opin. Genet. Dev. 15, 116–124 (2005). This step-by-step explanation describes the thermodynamic quantitative modelling of regulatory arrangements.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Segal, E. et al. Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data. Nat. Genet. 34, 166–176 (2003).

    CAS  PubMed  Google Scholar 

  145. Fraser, C. M. et al. The minimal gene complement of Mycoplasma genitalium. Science 270, 397–404 (1995).

    CAS  PubMed  Google Scholar 

  146. Dorman, C. J. Regulation of transcription by DNA supercoiling in Mycoplasma genitalium: global control in the smallest known self-replicating genome. Mol. Microbiol. 81, 302–304 (2011).

    CAS  PubMed  Google Scholar 

  147. Zhang, W. & Baseman, J. B. Transcriptional regulation of MG149, an osmoinducible lipoprotein gene from Mycoplasma genitalium. Mol. Microbiol. 81, 327–339 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Roth, C. W. & Nester, E. W. Co-ordinate control of tryptophan, histidine and tyrosine enzyme synthesis in Bacillus subtilis. J. Mol. Biol. 62, 577–589 (1971).

    CAS  PubMed  Google Scholar 

  149. Salgado, H., Moreno-Hagelsieb, G., Smith, T. F. & Collado-Vides, J. Operons in Escherichia coli: genomic analyses and predictions. Proc. Natl Acad. Sci. USA 97, 6652–6657 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Monod, J., Changeux, J. P. & Jacob, F. Allosteric proteins and cellular control systems. J. Mol. Biol. 6, 306–329 (1963).

    CAS  PubMed  Google Scholar 

  151. Jacob, F. Genetics of the bacterial cell. Science 152, 1470–1478 (1966).

    CAS  PubMed  Google Scholar 

  152. Bockhorst, J. et al. Predicting bacterial transcription units using sequence and expression data. Bioinformatics 19(Suppl. 1), i34–i43 (2003).

    PubMed  Google Scholar 

  153. Mao, X. et al. DOOR 2.0: presenting operons and their functions through dynamic and integrated views. Nucleic Acids Res. 42, 654–659 (2014).

    Google Scholar 

  154. Koide, T. et al. Prevalence of transcription promoters within archaeal operons and coding sequences. Mol. Syst. Biol. 5, 1–16 (2009).

    Google Scholar 

  155. Pray, L. A. What is a gene? Colinearity and transcription units. Nat. Educ. 1, 97 (2008).

    Google Scholar 

  156. Cho, B. et al. The transcription unit architecture of the Escherichia coli genome. Nat. Biotechnol. 27, 1043–1049 (2009).

    CAS  PubMed  Google Scholar 

  157. Liu, J. & Turnbough, C. L. Effects of transcriptional start site sequence and position on nucleotide-sensitive selection of alternative start sites at the pyrC promoter in Escherichia coli. J. Bacteriol. 176, 2938–2945 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Goldman, S. R. et al. NanoRNAs prime transcription initiation in vivo. Mol. Cell 42, 817–825 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Ciampi, M. S. Rho-dependent terminators and transcription termination. Microbiology 152, 2515–2528 (2006).

    CAS  PubMed  Google Scholar 

  160. Lau, L. F. & Roberts, J. W. Rho-dependent transcription termination at lambda R1 requires upstream sequences. J. Biol. Chem. 260, 574–584 (1985).

    CAS  PubMed  Google Scholar 

  161. Richardson, L. V. & Richardson, J. P. Rho-dependent termination of transcription is governed primarily by the upstream rho utilization (rut) sequences of a terminator. J. Biol. Chem. 271, 21597–21603 (1996).

    CAS  PubMed  Google Scholar 

  162. Jeong, K. S., Ahn, J. & Khodursky, A. B. Spatial patterns of transcriptional activity in the chromosome of Escherichia coli. Genome Biol. 5, (2004).

  163. Junier, I., Unal, E. B., Yus, E., Lloréns-Rico, V. & Serrano, L. Insights into the mechanisms of basal coordination of transcription using a genome-reduced bacterium. Cell Syst. 2, 391–401 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Yan, B., Boitano, M., Clark, T. A. & Ettwiller, L. SMRT-cappable-seq reveals complex operon variants in bacteria. Nat. Commun. 9, 3676 (2018). This study reports the identification of transcription units using long-read sequencing.

    PubMed  PubMed Central  Google Scholar 

  165. Bauerle, R. H. & Margolin, P. Evidence for two sites for initiation of gene expression in the tryptophan operon of Salmonella typhimurium. J. Mol. Biol. 26, 423–436 (1967).

    CAS  PubMed  Google Scholar 

  166. Ueno-Nishio, S., Backman, K. C. & Magasanik, B. Regulation at the glnL-operator-promoter of the complex glnALG operon of Escherichia coli. J. Bacteriol. 153, 1247–1251 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Conway, T. et al. Unprecedented high-resolution view of bacterial operon architecture revealed by RNA sequencing. MBio 5, e01442-14 (2014).

    PubMed  PubMed Central  Google Scholar 

  168. Li, S., Dong, X. & Su, Z. Directional RNA-seq reveals highly complex condition-dependent transcriptomes in E. coli K12 through accurate full-length transcripts assembling. BMC Genomics 14, 1–24 (2013).

    Google Scholar 

  169. Mao, X. et al. Revisiting operons: an analysis of the landscape of transcriptional units in E. coli. BMC Bioinformatics 16, 1–9 (2015).

    Google Scholar 

  170. Ju, X., Li, D. & Liu, S. Full-length RNA profiling reveals pervasive bidirectional transcription terminators in bacteria. Nat. Microbiol. 4, 1907–1918 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Sharma, C. M. et al. The primary transcriptome of the major human pathogen Helicobacter pylori. Nature 464, 250–255 (2010).

    CAS  PubMed  Google Scholar 

  172. Lybecker, M., Bilusic, I. & Raghavan, R. Pervasive transcription: detecting functional RNAs in bacteria. Transcription 5, e944039 (2014).

    PubMed  PubMed Central  Google Scholar 

  173. Wade, J. T. & Grainger, D. C. Pervasive transcription: illuminating the dark matter of bacterial transcriptomes. Nat. Rev. Microbiol. 12, 647–653 (2014).

    CAS  PubMed  Google Scholar 

  174. Price, M. N. et al. Indirect and suboptimal control of gene expression is widespread in bacteria. Mol. Syst. Biol. 9, 1–18 (2013).

    Google Scholar 

  175. Price, M. N., Wetmore, K. M., Deutschbauer, A. M. & Arkin, A. P. A comparison of the costs and benefits of bacterial gene expression. PLoS One 11, 1–22 (2016).

    Google Scholar 

  176. Shao, W., Price, M. N., Deutschbauer, A. M., Romine, M. F. & Arkin, A. P. Conservation of transcription start sites within genes across a bacterial genus. MBio 5, 1–13 (2014).

    Google Scholar 

  177. Wade, J. T. & Grainger, D. C. Spurious transcription and its impact on cell function. Transcription 9, 182–189 (2018).

    CAS  PubMed  Google Scholar 

  178. Pannier, L., Merino, E., Marchal, K. & Collado-Vides, J. Effect of genomic distance on coexpression of coregulated genes in E. coli. PLoS One 12, e0174887 (2017).

    PubMed  PubMed Central  Google Scholar 

  179. Stringer, A. M. et al. Genome-scale analyses of Escherichia coli and Salmonella enterica AraC reveal noncanonical targets and an expanded core regulon. J. Bacteriol. 196, 660–671 (2014).

    PubMed  PubMed Central  Google Scholar 

  180. Chen, Y.-J. et al. Characterization of 582 natural and synthetic terminators and quantification of their design constraints. Nat. Methods 10, 659–664 (2013).

    CAS  PubMed  Google Scholar 

  181. Maas, W. K. & Clark, A. J. Studies on the mechanism of repression of arginine biosynthesis in Escherichia coli: II. Dominance of repressibility in diploids. J. Mol. Biol. 8, 365–370 (1964).

    CAS  PubMed  Google Scholar 

  182. Ledezma-Tejeida, D., Altamirano-Pacheco, L., Fajardo, V. & Collado-Vides, J. Limits to a classic paradigm: most transcription factors in E. coli regulate genes involved in multiple biological processes. Nucleic Acids Res. 47, 6656–6667 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Pittard, J. & Yang, J. Biosynthesis of the aromatic amino acids. EcoSal Plus 3, 1–39 (2008).

    Google Scholar 

  184. Smith, M. W. & Neidhardt, F. C. Proteins induced by aerobiosis in Escherichia coli. J. Bacteriol. 154, 336–343 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Schaefer, E. M., Hartz, D., Gold, L. & Simoni, R. D. Ribosome-binding sites and RNA-processing sites in the transcript of the Escherichia coli unc operon. J. Bacteriol. 171, 3901–3908 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Monod, J., Wyman, J. & Changeux, J.-P. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12, 88–118 (1965). This study describes the classic, elegant model of allosteric transitions.

    CAS  PubMed  Google Scholar 

  187. Hoch, J. A. Two-component and phosphorelay signal transduction. Curr. Opin. Microbiol. 3, 165–170 (2000).

    CAS  PubMed  Google Scholar 

  188. Grundy, F. J. & Henkin, T. M. Regulation of gene expression by effectors that bind to RNA. Curr. Opin. Microbiol. 7, 126–131 (2004).

    CAS  PubMed  Google Scholar 

  189. Horii, T. et al. Regulation of SOS functions: purification of E. coli LexA protein and determination of its specific site cleaved by the RecA protein. Cell 27, 515–522 (1981).

    CAS  PubMed  Google Scholar 

  190. Jenal, U. & Hengge-Aronis, R. Regulation by proteolysis in bacterial cells. Curr. Opin. Microbiol. 6, 163–172 (2003).

    CAS  PubMed  Google Scholar 

  191. Uphoff, S. et al. Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation. Science 351, 1094–1097 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Takinowaki, H., Matsuda, Y., Yoshida, T., Kobayashi, Y. & Ohkubo, T. The solution structure of the methylated form of the N-terminal 16-kDa domain of Escherichia coli Ada protein. Protein Sci. 15, 487–497 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  193. Kotte, O., Zaugg, J. B. & Heinemann, M. Bacterial adaptation through distributed sensing of metabolic fluxes. Mol. Syst. Biol. 6, 1–9 (2010).

    Google Scholar 

  194. Mekalanos, J. J. Environmental signals controlling expression of virulence determinants in bacteria. J. Bacteriol. 174, 1–7 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Maurelli, A. T. Temperature regulation of virulence genes in pathogenic bacteria: a general strategy for human pathogens? Microb. Pathog. 7, 1–10 (1989).

    CAS  PubMed  Google Scholar 

  196. Miller, J. F., Mekalanos, J. J. & Falkow, S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science 243, 1355–1362 (1989).

    Google Scholar 

  197. Hurme, R., Berndt, K. D., Normark, S. J. & Rhen, M. A proteinaceous gene regulatory thermometer in Salmonella. Cell 90, 55–64 (1997).

    CAS  PubMed  Google Scholar 

  198. Piraner, D. I., Abedi, M. H., Moser, B. A., Lee-Gosselin, A. & Shapiro, M. G. Tunable thermal bioswitches for in vivo control of microbial therapeutics. Nat. Chem. Biol. 13, 75–80 (2017).

    CAS  PubMed  Google Scholar 

  199. Lindner, R. et al. Photoactivation mechanism of a bacterial light-regulated adenylyl cyclase. J. Mol. Biol. 429, 1336–1351 (2017).

    CAS  PubMed  Google Scholar 

  200. Winkler, A. et al. A ternary AppA-PpsR-DNA complex mediates light regulation of photosynthesis-related gene expression. Nat. Struct. Mol. Biol. 20, 859–867 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Smith, B., Kumar, A. & Bittner, T. Basic Formal Ontology for Bioinformatics (IFOMIS Reports, 2005).

  202. Strainic, M. G., Sullivan, J. J., Collado-Vides, J. & DeHaseth, P. L. Promoter interference in a bacteriophage lambda control region: effects of a range of interpromoter distances. J. Bacteriol. 182, 216–220 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  203. Scherrer, K. Primary transcripts: from the discovery of RNA processing to current concepts of gene expression—review. Exp. Cell Res. 373, 1–33 (2018).

    CAS  PubMed  Google Scholar 

  204. Sanchez-Vazquez, P., Dewey, C. N., Kitten, N., Ross, W. & Gourse, R. L. Genome-wide effects on Escherichia coli transcription from ppGpp binding to its two sites on RNA polymerase. Proc. Natl Acad. Sci. USA 116, 8310–8319 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Browning, D. F., Butala, M. & Busby, S. J. W. Bacterial transcription factors: regulation by Pick ‘N’ Mix. J. Mol. Biol. 431, 4067–4077 (2019).

    CAS  PubMed  Google Scholar 

  206. Haugen, S. P. et al. rRNA promoter regulation by nonoptimal binding of σ region 1.2: an additional recognition element for RNA polymerase. Cell 125, 1069–1082 (2006).

    CAS  PubMed  Google Scholar 

  207. Josaitis, C. A., Gaal, T. & Gourse, R. L. Stringent control and growth-rate-dependent control have nonidentical promoter sequence requirements. Proc. Natl Acad. Sci. USA 92, 1117–1121 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Davis, M. C., Kesthely, C. A., Franklin, E. A. & MacLellan, S. R. The essential activities of the bacterial sigma factor. Can. J. Microbiol. 63, 89–99 (2017).

    CAS  PubMed  Google Scholar 

  209. Ho, Y. Sen, Wulff, D. L. & Rosenberg, M. Bacteriophage λ protein cII binds promoters on the opposite face of the DNA helix from RNA polymerase. Nature 304, 703–708 (1983).

    CAS  PubMed  Google Scholar 

  210. Buck, M. & Cannon, W. Specific binding of the transcription factor sigma-54 to promoter DNA. Nature 358, 422–424 (1992).

    CAS  PubMed  Google Scholar 

  211. Seo, S. W. et al. Revealing genome-scale transcriptional regulatory landscape of OmpR highlights its expanded regulatory roles under osmotic stress in Escherichia coli K-12 MG1655. Sci. Rep. 7, 1–10 (2017).

    Google Scholar 

  212. Cho, B. K., Federowicz, S., Park, Y. S., Zengler, K. & Palsson, B. Deciphering the transcriptional regulatory logic of amino acid metabolism. Nat. Chem. Biol. 8, 65–71 (2012).

    CAS  Google Scholar 

  213. Cho, B. K. et al. The PurR regulon in Escherichia coli K-12 MG1655. Nucleic Acids Res. 39, 6456–6464 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Kim, D. et al. Systems assessment of transcriptional regulation on central carbon metabolism by Cra and CRP. Nucleic Acids Res. 46, 2901–2917 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. Seo, S. W. et al. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli. Nat. Commun. 5, 1–10 (2014).

    Google Scholar 

  216. Seo, S. W., Kim, D., O’Brien, E. J., Szubin, R. & Palsson, B. O. Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli. Nat. Commun. 6, 1–8 (2015).

    Google Scholar 

  217. Seo, S. W., Kim, D., Szubin, R. & Palsson, B. O. Genome-wide reconstruction of OxyR and SoxRS transcriptional regulatory networks under oxidative stress in Escherichia coli K-12 MG1655. Cell Rep. 12, 1289–1299 (2015).

    CAS  PubMed  Google Scholar 

  218. Grainger, D. C., Aiba, H., Hurd, D., Browning, D. F. & Busby, S. J. W. Transcription factor distribution in Escherichia coli: studies with FNR protein. Nucleic Acids Res. 35, 269–278 (2007).

  219. Partridge, J. D., Bodenmiller, D. M., Humphrys, M. S. & Spiro, S. NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility. Mol. Microbiol. 73, 680–694 (2009).

  220. Grainger, D. C., Hurd, D., Goldberg, M. D. & Busby, S. J. W. Association of nucleoid proteins with coding and non-coding segments of the Escherichia coli genome. Nucleic Acids Res. 34, 4642–4652 (2006).

  221. Sogaard-Andersen, L., Mellegaard, N. E., Douthwaite, S. R. & Valentin-Hansen, P. Tandem DNA-bound cAMP–CRP complexes are required for transcriptional repression of the deoP2 promoter by the CytR repressor in Escherichia coli. Mol. Microbiol. 4, 1595–1601 (1990).

    PubMed  Google Scholar 

  222. Tao, H., Hasona, A., Do, P. M., Ingram, L. O. & Shanmugam, K. T. Global gene expression analysis revealed an unsuspected deo operon under the control of molybdate sensor, ModE protein, in Escherichia coli. Arch. Microbiol. 184, 225–233 (2005).

    CAS  PubMed  Google Scholar 

  223. González-Gil, G., Bringmann, P. & Kahmann, R. FIS is a regulator of metabolism in Escherichia coli. Mol. Microbiol. 22, 21–29 (1996).

    PubMed  Google Scholar 

  224. Valentin-Hansen, P., Albrechtsen, B. & Løve Larsen, J. E. DNA–protein recognition: demonstration of three genetically separated operator elements that are required for repression of the Escherichia coli deoCABD promoters by the DeoR repressor. EMBO J. 5, 2015–2021 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  225. Barnard, A., Wolfe, A. & Busby, S. Regulation at complex bacterial promoters: how bacteria use different promoter organizations to produce different regulatory outcomes. Curr. Opin. Microbiol. 7, 102–108 (2004).

    CAS  PubMed  Google Scholar 

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Acknowledgements

C.M.-A. is a doctoral student from the Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM), and has received CONACyT fellowship 576333. J.C.-V. acknowledges funding by Universidad Nacional Autónoma de México (UNAM) and the National Institutes of Health (5R01GM110597-04, 1RO1GM131643-01A1 and R01GM077678). J.C.-V. acknowledges being on sabbatical leave at the Center for Genomic Regulation, Barcelona, Spain. B.O.P. acknowledges the support of the Galletti Endowment at UC San Diego. The authors acknowledge J. Soffer, S. Gama-Castro and H. Salgado for useful discussions, and D. W. Sant for updating the definitions in Sequence Ontology. The authors also acknowledge the highly valuable suggestions from the referees.

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C.M.-A. researched the literature. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S., K.E., B.O.P., J.E.G. and J.C.-V. provided substantial contributions to discussions of the content. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S. and J.C.-V. wrote the article. C.M.-A., S.J.W.B., J.T.W., J.v.H., A.P.A., G.D.S., K.E., B.O.P. and J.C.-V. reviewed and/or edited the manuscript before submission.

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Correspondence to Julio Collado-Vides.

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Related links

Basic Formal Ontology: https://basic-formal-ontology.org/

EcoCyc: https://ecocyc.org

RegulonDB: http://regulondb.ccg.unam.mx/

RegulonDB Gensor Unit Groups: http://regulondb.ccg.unam.mx/central_panel_menu/integrated_views_and_tools/gensor_unit_groups

Sequence Ontology: http://www.sequenceontology.org

Supplementary information

Glossary

Activators

Gene products that increase transcription, indicating that their function is to enhance promoter activity.

Repressors

Gene products that decrease transcription, indicating that their function is to hamper promoter activity.

Operator

A genetic entity adjacent to a group of genes that regulates their expression and is sensitive to a repressor.

Operon

A set of adjacent co-transcribed genes.

Motifs

Representations of a collection of binding sites that summarize the binding-site characteristics.

Transcriptional pausing

A process through which the RNA polymerase slows down transcription during elongation.

5′-Rapid amplification of cDNA ends

(5′-RACE). A method to amplify mRNA between a defined internal site and its initiation site.

Global regulators

Transcription factors that affect a large number of genes involved in many different functions.

DNA supercoiling

The writhe of DNA over the double-stranded axis.

Monocistronic operons

Operons that encode a single gene product.

Transcriptional read-through

Transcription that allows RNA polymerase to continue transcription beyond termination sites.

Stimulons

Sets of genes whose products are increased in response to a common environmental stimulus.

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Mejía-Almonte, C., Busby, S.J.W., Wade, J.T. et al. Redefining fundamental concepts of transcription initiation in bacteria. Nat Rev Genet 21, 699–714 (2020). https://doi.org/10.1038/s41576-020-0254-8

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