Transcription initiation involves the interaction of DNA-dependent RNA polymerase with promoters. In bacteria, this is a highly regulated process.
Many regulators interact directly with the bacterial DNA-dependent RNA polymerase, whereas other regulators interact directly with promoters.
Regulation of transcription initiation occurs in the context of folding and compaction of bacterial chromosomes.
A very wide range of different strategies are used to regulate transcription initiation in bacteria and these differ between species.
Gene expression in bacteria relies on promoter recognition by the DNA-dependent RNA polymerase and subsequent transcription initiation. Bacterial cells are able to tune their transcriptional programmes to changing environments, through numerous mechanisms that regulate the activity of RNA polymerase, or change the set of promoters to which the RNA polymerase can bind. In this Review, we outline our current understanding of the different factors that direct the regulation of transcription initiation in bacteria, whether by interacting with promoters, with RNA polymerase or with both, and we discuss the diverse molecular mechanisms that are used by these factors to regulate gene expression.
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Browning, D. F. & Busby, S. J. The regulation of bacterial transcription initiation. Nat. Rev. Microbiol. 2, 57–65 (2004).
Feklistov, 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).
Murakami, K. S. & Darst, S. A. Bacterial RNA polymerases: the wholo story. Curr. Opin. Struct. Biol. 13, 31–39 (2003).
Feklistov, A. & Darst, S. A. Structural basis for promoter −10 element recognition by the bacterial RNA polymerase sigma subunit. Cell 147, 1257–1269 (2011).
Zhang, Y. et al. Structural basis of transcription initiation. Science 338, 1076–1080 (2012). This work complements previous structural work detailed in reference 3 by revealing the interactions of bacterial holoenzyme containing σ70 with the downstream end of the initiation 'bubble'. The results introduce us to unstacking of certain bases and their insertion into pockets in the sigma factor, and to specific interactions between side chains in the core enzyme and certain bases near the transcript start (the core recognition element (CRE)).
Zuo, Y. & Steitz, T. A. Crystal structures of the E. coli transcription initiation complexes with a complete bubble. Mol. Cell 58, 534–540 (2015).
Bae, B., Feklistov, A., Lass-Napiorkowska, A., Landick, R. & Darst, S. A. Structure of a bacterial RNA polymerase holoenzyme open promoter complex. eLife 4, e08504 (2015).
Ruff, E. F., Record, M. T. & Artsimovitch, I. Initial events in bacterial transcription initiation. Biomolecules 5, 1035–1062 (2015).
Washburn, R. S. & Gottesman, M. E. Regulation of transcription elongation and termination. Biomolecules 5, 1063–1078 (2015).
Roberts, J. W., Shankar, S. & Filter, J. J. RNA polymerase elongation factors. Annu. Rev. Microbiol. 62, 211–233 (2008).
Zhang, J. & Landick, R. A two-way street: regulatory interplay between RNA polymerase and nascent RNA structure. Trends Biochem. Sci. 41, 293–310 (2016).
Campbell, E. A. et al. Structure of the bacterial RNA polymerase promoter specificity sigma subunit. Mol. Cell 9, 527–539 (2002).
Mekler, V. et al. Structural organization of bacterial RNA polymerase holoenzyme and the RNA polymerase–promoter open complex. Cell 108, 599–614 (2002).
Bae, B. et al. Phage T7 Gp2 inhibition of Escherichia coli RNA polymerase involves misappropriation of σ70 domain 1.1. Proc. Natl Acad. Sci. USA 110, 19772–19777 (2013).
Murakami, K. S. X-ray crystal structure of Escherichia coli RNA polymerase σ70 holoenzyme. J. Biol. Chem. 288, 9126–9134 (2013).
Gruber, T. M. & Gross, C. A. Multiple sigma subunits and the partitioning of bacterial transcription space. Annu. Rev. Microbiol. 57, 441–466 (2003).
Murakami, K. S., Masuda, S., Campbell, E. A., Muzzin, O. & Darst, S. A. Structural basis of transcription initiation: an RNA polymerase holoenzyme–DNA complex. Science 296, 1285–1290 (2002).
Vassylyev, D. G. et al. Crystal structure of a bacterial RNA polymerase holoenzyme at 2.6 Å resolution. Nature 417, 712–719 (2002).
Yang, Y. et al. Structures of the RNA polymerase–σ54 reveal new and conserved regulatory strategies. Science 349, 882–885 (2015). This paper presents the long awaited structure of σ54 and its interactions with RNA polymerase. The structure shows how σ54 really is different from σ70, why it is incompetent for transcription initiation, and suggests how its activators might work.
Jishage, M. & Ishihama, A. Regulation of RNA polymerase sigma subunit synthesis in Escherichia coli: intracellular levels of σ70 and σ38. J. Bacteriol. 177, 6832–6835 (1995).
Jishage, M., Iwata, A., Ueda, S. & Ishihama, A. Regulation of RNA polymerase sigma subunit synthesis in Escherichia coli: intracellular levels of four species of sigma subunit under various growth conditions. J. Bacteriol. 178, 5447–5451 (1996).
Maeda, H., Fujita, N. & Ishihama, A. Competition among seven Escherichia coli sigma subunits: relative binding affinities to the core RNA polymerase. Nucleic Acids Res. 28, 3497–3503 (2000).
Campbell, E. A., Westblade, L. F. & Darst, S. A. Regulation of bacterial RNA polymerase sigma factor activity: a structural perspective. Curr. Opin. Microbiol. 11, 121–127 (2008).
Rhodius, V. A. et al. Design of orthogonal genetic switches based on a crosstalk map of sigmas, anti-sigmas, and promoters. Mol. Syst. Biol. 9, 702 (2013).
Campagne, S., Marsh, M. E., Capitani, G., Vorholt, J. A. & Allain, F. H. Structural basis for −10 promoter element melting by environmentally induced sigma factors. Nat. Struct. Mol. Biol. 21, 269–276 (2014).
Koo, B. M., Rhodius, V. A., Nonaka, G., deHaseth, P. L. & Gross, C. A. Reduced capacity of alternative sigmas to melt promoters ensures stringent promoter recognition. Genes Dev. 23, 2426–2436 (2009).
Hollands, K., Lee, D. J., Lloyd, G. S. & Busby, S. J. Activation of σ28-dependent transcription in Escherichia coli by the cyclic AMP receptor protein requires an unusual promoter organization. Mol. Microbiol. 75, 1098–1111 (2010).
Paget, M. S. Bacterial sigma factors and anti-sigma factors: structure, function and distribution. Biomolecules 5, 1245–1265 (2015).
Osterberg, S., del Peso-Santos, T. & Shingler, V. Regulation of alternative sigma factor use. Annu. Rev. Microbiol. 65, 37–55 (2011).
Francez-Charlot, A. et al. Sigma factor mimicry involved in regulation of general stress response. Proc. Natl Acad. Sci. USA 106, 3467–3472 (2009). Following the resolution of structures of sigma–anti-sigma complexes detailed in reference 23, this paper reports that an anti-anti-sigma factor can function by mimicking a sigma factor. Although predictable that this would be the case, its formal demonstration was a landmark for the field.
Herrou, J., Rotskoff, G., Luo, Y., Roux, B. & Crosson, S. Structural basis of a protein partner switch that regulates the general stress response of α-proteobacteria. Proc. Natl Acad. Sci. USA 109, E1415–E1423 (2012).
Typas, A., Barembruch, C., Possling, A. & Hengge, R. Stationary phase reorganisation of the Escherichia coli transcription machinery by Crl protein, a fine-tuner of sigmas activity and levels. EMBO J. 26, 1569–1578 (2007).
Banta, A. B. et al. Key features of σS required for specific recognition by Crl, a transcription factor promoting assembly of RNA polymerase holoenzyme. Proc. Natl Acad. Sci. USA 110, 15955–15960 (2013).
Banta, A. B. et al. Structure of the RNA polymerase assembly factor Crl and identification of its interaction surface with σS. J. Bacteriol. 196, 3279–3288 (2014).
Yuan, A. H. et al. Rsd family proteins make simultaneous interactions with regions 2 and 4 of the primary sigma factor. Mol. Microbiol. 70, 1136–1151 (2008).
Piper, S. E., Mitchell, J. E., Lee, D. J. & Busby, S. J. A global view of Escherichia coli Rsd protein and its interactions. Mol. Biosyst. 5, 1943–1947 (2009).
Sharma, U. K. & Chatterji, D. Transcriptional switching in Escherichia coli during stress and starvation by modulation of σ70 activity. FEMS Microbiol. Rev. 34, 646–657 (2010).
Jishage, M., Kvint, K., Shingler, V. & Nystrom, T. Regulation of sigma factor competition by the alarmone ppGpp. Genes Dev. 16, 1260–1270 (2002).
Costanzo, A. et al. ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor σE in Escherichia coli by both direct and indirect mechanisms. Mol. Microbiol. 67, 619–632 (2008).
Merrick, M. J. In a class of its own — the RNA polymerase sigma factor σ54 (σN). Mol. Microbiol. 10, 903–909 (1993).
Studholme, D. J. & Buck, M. The biology of enhancer-dependent transcriptional regulation in bacteria: insights from genome sequences. FEMS Microbiol. Lett. 186, 1–9 (2000).
Wigneshweraraj, S. et al. Modus operandi of the bacterial RNA polymerase containing the σ54 promoter-specificity factor. Mol. Microbiol. 68, 538–546 (2008).
Flentie, K., Garner, A. L. & Stallings, C. L. The Mycobacterium tuberculosis transcription machinery: ready to respond to host attacks. J. Bacteriol. 198, 1360–1373 (2016).
Hubin, E. A. et al. Structural, functional, and genetic analyses of the actinobacterial transcription factor RbpA. Proc. Natl Acad. Sci. USA 112, 7171–7176 (2015).
Srivastava, D. B. et al. Structure and function of CarD, an essential mycobacterial transcription factor. Proc. Natl Acad. Sci. USA 110, 12619–12624 (2013).
Bae, B. et al. CarD uses a minor groove wedge mechanism to stabilize the RNA polymerase open promoter complex. eLife 4, e08505 (2015).
Perederina, A. et al. Regulation through the secondary channel — structural framework for ppGpp–DksA synergism during transcription. Cell 118, 297–309 (2004).
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).
Paul, B. J., Berkmen, M. B. & Gourse, R. L. DksA potentiates direct activation of amino acid promoters by ppGpp. Proc. Natl Acad. Sci. USA 102, 7823–7828 (2005). In this study, an in vitro assay is used to provide the proof that ppGpp, together with DksA, really can directly stimulate transcription initiation at a promoter. This paper provides a wonderful lesson in how the limitations of genetics can be atoned for by amazing biochemistry.
Lennon, C. W. et al. Direct interactions between the coiled-coil tip of DksA and the trigger loop of RNA polymerase mediate transcriptional regulation. Genes Dev. 26, 2634–2646 (2012).
Ross, W., Vrentas, C. E., Sanchez-Vazquez, P., Gaal, T. & Gourse, R. L. The magic spot: a ppGpp binding site on E. coli RNA polymerase responsible for regulation of transcription initiation. Mol. Cell 50, 420–429 (2013).
Hauryliuk, V., Atkinson, G. C., Murakami, K. S., Tenson, T. & Gerdes, K. Recent functional insights into the role of (p)ppGpp in bacterial physiology. Nat. Rev. Microbiol. 13, 298–309 (2015).
Zenkin, N. & Yuzenkova, Y. New insights into the functions of transcription factors that bind the RNA polymerase secondary channel. Biomolecules 5, 1195–1209 (2015).
Yuzenkova, Y., Roghanian, M. & Zenkin, N. Multiple active centers of multi-subunit RNA polymerases. Transcription 3, 115–118 (2012).
Friedman, L. J. & Gelles, J. Multi-wavelength single-molecule fluorescence analysis of transcription mechanisms. Methods 86, 27–36 (2015).
Zhang, Y. et al. DksA guards elongating RNA polymerase against ribosome-stalling-induced arrest. Mol. Cell 53, 766–778 (2014).
Cavanagh, A. T. & Wassarman, K. M. 6S RNA, a global regulator of transcription in Escherichia coli. Bacillus subtilis, and beyond. Annu. Rev. Microbiol. 68, 45–60 (2014).
Liu, B. et al. A bacteriophage transcription regulator inhibits bacterial transcription initiation by sigma-factor displacement. Nucleic Acids Res. 42, 4294–4305 (2014).
Lambert, L. J., Wei, Y., Schirf, V., Demeler, B. & Werner, M. H. T4 AsiA blocks DNA recognition by remodeling σ70 region 4. EMBO J. 23, 2952–2962 (2004).
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).
Hinton, D. M. Transcriptional control in the prereplicative phase of T4 development. Virol. J. 7, 289 (2010).
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).
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).
Zuber, P. Management of oxidative stress in Bacillus. Annu. Rev. Microbiol. 63, 575–597 (2009).
Newberry, K. J., Nakano, S., Zuber, P. & Brennan, R. G. Crystal structure of the Bacillus subtilis anti-alpha, global transcriptional regulator, Spx, in complex with the α C-terminal domain of RNA polymerase. Proc. Natl Acad. Sci. USA 102, 15839–15844 (2005).
Lamour, V., Westblade, L. F., Campbell, E. A. & Darst, S. A. Crystal structure of the in vivo-assembled Bacillus subtilis Spx/RNA polymerase α subunit C-terminal domain complex. J. Struct. Biol. 168, 352–356 (2009).
Mangel, W. F. & Chamberlin, M. J. Studies of ribonucleic acid chain initiation by Escherichia coli ribonucleic acid polymerase bound to T7 deoxyribonucleic acid. I. An assay for the rate and extent of ribonucleic acid chain initiation. J. Biol. Chem. 249, 2995–3001 (1974).
Murray, H. D., Schneider, D. A. & Gourse, R. L. Control of rRNA expression by small molecules is dynamic and nonredundant. Mol. Cell 12, 125–134 (2003).
Schneider, D. A., Gaal, T. & Gourse, R. L. NTP-sensing by rRNA promoters in Escherichia coli is direct. Proc. Natl Acad. Sci. USA 99, 8602–8607 (2002).
Krasny, L. & Gourse, R. L. An alternative strategy for bacterial ribosome synthesis: Bacillus subtilis rRNA transcription regulation. EMBO J. 23, 4473–4483 (2004).
Liu, K., Bittner, A. N. & Wang, J. D. Diversity in (p)ppGpp metabolism and effectors. Curr. Opin. Microbiol. 24, 72–79 (2015). This study provides a very clear account of how ppGpp (and pppGpp) has different roles in different bacteria. A warning that what is true for E. coli may not be true for other bacteria, let alone elephants.
Turnbough, C. L. & Switzer, R. L. Regulation of pyrimidine biosynthetic gene expression in bacteria: repression without repressors. Microbiol. Mol. Biol. Rev. 72, 266–300 (2008).
Martinez-Antonio, A. & Collado-Vides, J. Identifying global regulators in transcriptional regulatory networks in bacteria. Curr. Opin. Microbiol. 6, 482–489 (2003).
Ishihama, A. Prokaryotic genome regulation: a revolutionary paradigm. Proc. Jpn Acad. Ser. B Phys. Biol. Sci. 88, 485–508 (2012).
Cho, B. K., Palsson, B. & Zengler, K. Deciphering the regulatory codes in bacterial genomes. Biotechnol. J. 6, 1052–1063 (2011).
Salgado, H. et al. Extracting regulatory networks of Escherichia coli from RegulonDB. Methods Mol. Biol. 804, 179–195 (2012).
Dillon, S. C. & Dorman, C. J. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat. Rev. Microbiol. 8, 185–195 (2010).
Ali Azam, T., Iwata, A., Nishimura, A., Ueda, S. & Ishihama, A. Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. J. Bacteriol. 181, 6361–6370 (1999).
Azam, T. A. & Ishihama, A. Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity. J. Biol. Chem. 274, 33105–33113 (1999).
Luijsterburg, M. S., Noom, M. C., Wuite, G. J. & Dame, R. T. The architectural role of nucleoid-associated proteins in the organization of bacterial chromatin: a molecular perspective. J. Struct. Biol. 156, 262–272 (2006).
Browning, D. F., Grainger, D. C. & Busby, S. J. Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression. Curr. Opin. Microbiol. 13, 773–780 (2010).
Grainger, D. C., Goldberg, M. D., Lee, D. J. & Busby, S. J. Selective repression by Fis and H-NS at the Escherichia coli dps promoter. Mol. Microbiol. 68, 1366–1377 (2008).
Sobetzko, P., Glinkowska, M., Travers, A. & Muskhelishvili, G. DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle. Mol. Biosyst. 9, 1643–1651 (2013).
Sobetzko, P., Travers, A. & Muskhelishvili, G. Gene order and chromosome dynamics coordinate spatiotemporal gene expression during the bacterial growth cycle. Proc. Natl Acad. Sci. USA 109, E42–E50 (2012).
Dorman, C. J. Co-operative roles for DNA supercoiling and nucleoid-associated proteins in the regulation of bacterial transcription. Biochem. Soc. Trans. 41, 542–547 (2013).
Zhang, W. & Baseman, J. B. Transcriptional regulation of MG_149, an osmoinducible lipoprotein gene from Mycoplasma genitalium. Mol. Microbiol. 81, 327–339 (2011).
Neumann, S. & Quinones, A. Discoordinate gene expression of gyrA and gyrB in response to DNA gyrase inhibition in Escherichia coli. J. Basic Microbiol. 37, 53–69 (1997).
Lal, A. et al. Genome scale patterns of supercoiling in a bacterial chromosome. Nat. Commun. 7, 11055 (2016).
Bryant, J. A., Sellars, L. E., Busby, S. J. & Lee, D. J. Chromosome position effects on gene expression in Escherichia coli K-12. Nucleic Acids Res. 42, 11383–11392 (2014).
Swint-Kruse, L. & Matthews, K. S. Allostery in the LacI/GalR family: variations on a theme. Curr. Opin. Microbiol. 12, 129–137 (2009).
Semsey, S., Tolstorukov, M. Y., Virnik, K., Zhurkin, V. B. & Adhya, S. DNA trajectory in the Gal repressosome. Genes Dev. 18, 1898–1907 (2004).
Butala, M. et al. Double locking of an Escherichia coli promoter by two repressors prevents premature colicin expression and cell lysis. Mol. Microbiol. 86, 129–139 (2012).
Kamensek, S. et al. Silencing of DNase colicin E8 gene expression by a complex nucleoprotein assembly ensures timely colicin induction. PLoS Genet. 11, e1005354 (2015).
Valentin-Hansen, P., Sogaard-Andersen, L. & Pedersen, H. A flexible partnership: the CytR anti-activator and the cAMP–CRP activator protein, comrades in transcription control. Mol. Microbiol. 20, 461–466 (1996).
Monsalve, M., Mencia, M., Salas, M. & Rojo, F. Protein p4 represses phage Φ29 A2c promoter by interacting with the α subunit of Bacillus subtilis RNA polymerase. Proc. Natl Acad. Sci. USA 93, 8913–8918 (1996).
Lee, D. J., Minchin, S. D. & Busby, S. J. Activating transcription in bacteria. Annu. Rev. Microbiol. 66, 125–152 (2012).
Benoff, B. et al. Structural basis of transcription activation: the CAP–αCTD–DNA complex. Science 297, 1562–1566 (2002).
Gaston, K., Bell, A., Kolb, A., Buc, H. & Busby, S. Stringent spacing requirements for transcription activation by CRP. Cell 62, 733–743 (1990).
Zhou, Y., Kolb, A., Busby, S. J. & Wang, Y. P. Spacing requirements for class I transcription activation in bacteria are set by promoter elements. Nucleic Acids Res. 42, 9209–9216 (2014).
Dove, S. L., Huang, F. W. & Hochschild, A. Mechanism for a transcriptional activator that works at the isomerization step. Proc. Natl Acad. Sci. USA 97, 13215–13220 (2000).
Jain, D., Nickels, B. E., Sun, L., Hochschild, A. & Darst, S. A. Structure of a ternary transcription activation complex. Mol. Cell 13, 45–53 (2004).
Niu, W., Kim, Y., Tau, G., Heyduk, T. & Ebright, R. H. Transcription activation at class II CAP-dependent promoters: two interactions between CAP and RNA polymerase. Cell 87, 1123–1134 (1996).
Feng, Y., Zhang, Y. & Ebright, R. H. Structural basis of transcription activation. Science 352, 1330–1333 (2016). This paper describes the first full molecular picture of class II transcription activation at a target promoter, and contrasts with previous reports that have described components of the process.
Brown, N. L., Stoyanov, J. V., Kidd, S. P. & Hobman, J. L. The MerR family of transcriptional regulators. FEMS Microbiol. Rev. 27, 145–163 (2003).
Philips, S. J. et al. Allosteric transcriptional regulation via changes in the overall topology of the core promoter. Science 349, 877–881 (2015). Working with CueR, which senses copper and silver ions, this paper presents high-resolution structures of its complexes at a target sequence when in either activator or repressor mode. The results complement previous work detailed in reference 106 showing that DNA distortion by such factors is uneven.
Heldwein, E. E. & Brennan, R. G. Crystal structure of the transcription activator BmrR bound to DNA and a drug. Nature 409, 378–382 (2001).
Bustamante, V. H., Santana, F. J., Calva, E. & Puente, J. L. Transcriptional regulation of type III secretion genes in enteropathogenic Escherichia coli: Ler antagonizes H-NS-dependent repression. Mol. Microbiol. 39, 664–678 (2001).
Sperandio, V. et al. Activation of enteropathogenic Escherichia coli (EPEC) LEE2 and LEE3 operons by Ler. Mol. Microbiol. 38, 781–793 (2000).
Browning, D. F., Cole, J. A. & Busby, S. J. Transcription activation by remodelling of a nucleoprotein assembly: the role of NarL at the FNR-dependent Escherichia coli nir promoter. Mol. Microbiol. 53, 203–215 (2004).
Browning, D. F., Cole, J. A. & Busby, S. J. Regulation by nucleoid-associated proteins at the Escherichia coli nir operon promoter. J. Bacteriol. 190, 7258–7267 (2008).
Tyson, K. L., Cole, J. A. & Busby, S. J. Nitrite and nitrate regulation at the promoters of two Escherichia coli operons encoding nitrite reductase: identification of common target heptamers for both NarP- and NarL-dependent regulation. Mol. Microbiol. 13, 1045–1055 (1994).
Bush, M. & Dixon, R. The role of bacterial enhancer binding proteins as specialized activators of σ54-dependent transcription. Microbiol. Mol. Biol. Rev. 76, 497–529 (2012).
Buck, M. et al. A second paradigm for gene activation in bacteria. Biochem. Soc. Trans. 34, 1067–1071 (2006).
Casadesus, J. & Low, D. Epigenetic gene regulation in the bacterial world. Microbiol. Mol. Biol. Rev. 70, 830–856 (2006).
van der Woude, M. W. & Henderson, I. R. Regulation and function of Ag43 (flu). Annu. Rev. Microbiol. 62, 153–169 (2008).
Sanchez-Romero, M. A., Cota, I. & Casadesus, J. DNA methylation in bacteria: from the methyl group to the methylome. Curr. Opin. Microbiol. 25, 9–16 (2015).
van der Woude, M. W. & Baumler, A. J. Phase and antigenic variation in bacteria. Clin. Microbiol. Rev. 17, 581–611 (2004).
van der Woude, M. W. Phase variation: how to create and coordinate population diversity. Curr. Opin. Microbiol. 14, 205–211 (2011).
Cerdeno-Tarraga, A. M. et al. Extensive DNA inversions in the B. fragilis genome control variable gene expression. Science 307, 1463–1465 (2005).
Moxon, R., Bayliss, C. & Hood, D. Bacterial contingency loci: the role of simple sequence DNA repeats in bacterial adaptation. Annu. Rev. Genet. 40, 307–333 (2006).
Jacob, F. Evolution and tinkering. Science 196, 1161–1166 (1977).
Wade, J. T. & Grainger, D. C. Pervasive transcription: illuminating the dark matter of bacterial transcriptomes. Nat. Rev. Microbiol. 12, 647–653 (2014).
Grohmann, D. & Werner, F. Recent advances in the understanding of archaeal transcription. Curr. Opin. Microbiol. 14, 328–334 (2011).
Visweswariah, S. S. & Busby, S. J. 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).
Grainger, D. C., Hurd, D., Harrison, M., Holdstock, J. & Busby, S. J. 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).
Shimada, T., Ishihama, A., Busby, S. J. & 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).
Aiyar, S. E. et al. Architecture of Fis-activated transcription complexes at the Escherichia coli rrnB P1 and rrnE P1 promoters. J. Mol. Biol. 316, 501–516 (2002).
Rossiter, A. E. et al. Expression of different bacterial cytotoxins is controlled by two global transcription factors, CRP and Fis, that co-operate in a shared-recruitment mechanism. Biochem. J. 466, 323–335 (2015).
Lisser, S. & Margalit, H. Compilation of E. coli mRNA promoter sequences. Nucleic Acids Res. 21, 1507–1516 (1993).
Hook-Barnard, I. G. & Hinton, D. M. Transcription initiation by mix and match elements: flexibility for polymerase binding to bacterial promoters. Gene Regul. Syst. Bio 1, 275–293 (2007).
Ross, W., Ernst, A. & Gourse, R. L. Fine structure of E. coli RNA polymerase–promoter interactions: α subunit binding to the UP element minor groove. Genes Dev. 15, 491–506 (2001).
Sclavi, B. et al. Real-time characterization of intermediates in the pathway to open complex formation by Escherichia coli RNA polymerase at the T7A1 promoter. Proc. Natl Acad. Sci. USA 102, 4706–4711 (2005).
Davis, C. A., Bingman, C. A., Landick, R., Record, M. T. & Saecker, R. M. Real-time footprinting of DNA in the first kinetically significant intermediate in open complex formation by Escherichia coli RNA polymerase. Proc. Natl Acad. Sci. USA 104, 7833–7838 (2007).
Buckle, M., Pemberton, I. K., Jacquet, M. A. & Buc, H. The kinetics of sigma subunit directed promoter recognition by E. coli RNA polymerase. J. Mol. Biol. 285, 955–964 (1999).
Stracy, M. et al. Live-cell superresolution microscopy reveals the organization of RNA polymerase in the bacterial nucleoid. Proc. Natl Acad. Sci. USA 112, E4390–E4399 (2015). This study shows that live microscopy can be used to observe individual molecules of RNA polymerase in E. coli . This is a prerequisite for future direct observation of responses to regulatory triggers.
Patrick, M., Dennis, P. P., Ehrenberg, M. & Bremer, H. Free RNA polymerase in E. coli. Biochimie 119, 80–91 (2015).
Hsu, L. M. Promoter escape by Escherichia coli RNA polymerase. EcoSal Plus http://dx.doi.org/10.1128/ecosalplus.18.104.22.168 (2008).
Skancke, J., Bar, N., Kuiper, M. & Hsu, L. M. Sequence-dependent promoter escape efficiency is strongly influenced by bias for the pretranslocated state during initial transcription. Biochemistry 54, 4267–4275 (2015).
Bauer, D. L. V., Duchi, D. & Kapanidis, A. N. E. coli RNA polymerase pauses during initial transcription. Biophys. J. 110 (Suppl. 1), 21a (2016).
Reppas, N. B., Wade, J. T., Church, G. M. & Struhl, K. The transition between transcriptional initiation and elongation in E. coli is highly variable and often rate limiting. Mol. Cell 24, 747–757 (2006).
Sendy, B., Lee, D. J., Busby, S. J. & Bryant, J. A. RNA polymerase supply and flux through the lac operon in Escherichia coli. Philos. Trans. R. Soc. Lond. B. Biol. Sci. (in the press).
Jacob, F. La Statue Intérieure (in French) (Éditions Odile Jacob, 1987).
Müller-Hill, B. The lac Operon. A Short History of a Genetic Paradigm (Walter de Gruyter, 1996).
Schwartz, M. in Origins of Molecular Biology. A Tribute to Jacques Monod (eds Lwoff, A. & Ullmann, A.) 207–216 (Academic Press, 1979).
Cases, I. & de Lorenzo, V. The black cat/white cat principle of signal integration in bacterial promoters. EMBO J. 20, 1–11 (2001).
Pul, Ü. & Wagner, R. in Bacterial Chromatin (eds Dame, R. T. & Dorman, C. J.) 149–173 (Springer, 2010).
Dorman, C. J. H-NS: a universal regulator for a dynamic genome. Nat. Rev. Microbiol. 2, 391–400 (2004).
Stoebel, D. M., Free, A. & Dorman, C. J. Anti-silencing: overcoming H-NS-mediated repression of transcription in Gram-negative enteric bacteria. Microbiology 154, 2533–2545 (2008).
Ohniwa, R. L. et al. Dynamic state of DNA topology is essential for genome condensation in bacteria. EMBO J. 25, 5591–5602 (2006).
Micka, B. & Marahiel, M. A. The DNA-binding protein HBsu is essential for normal growth and development in Bacillus subtilis. Biochimie 74, 641–650 (1992).
Grove, A. Functional evolution of bacterial histone-like HU proteins. Curr. Issues Mol. Biol. 13, 1–12 (2011).
Ball, C. A., Osuna, R., Ferguson, K. C. & Johnson, R. C. Dramatic changes in Fis levels upon nutrient upshift in Escherichia coli. J. Bacteriol. 174, 8043–8056 (1992).
Dame, R. T., Noom, M. C. & Wuite, G. J. Bacterial chromatin organization by H-NS protein unravelled using dual DNA manipulation. Nature 444, 387–390 (2006).
Dame, R. T., Wyman, C. & Goosen, N. H-NS mediated compaction of DNA visualised by atomic force microscopy. Nucleic Acids Res. 28, 3504–3510 (2000).
Maurer, S., Fritz, J. & Muskhelishvili, G. A systematic in vitro study of nucleoprotein complexes formed by bacterial nucleoid-associated proteins revealing novel types of DNA organization. J. Mol. Biol. 387, 1261–1276 (2009).
Grainger, D. C., Hurd, D., Goldberg, M. D. & Busby, S. J. Association of nucleoid proteins with coding and non-coding segments of the Escherichia coli genome. Nucleic Acids Res. 34, 4642–4652 (2006).
Kahramanoglou, C. et al. Direct and indirect effects of H-NS and Fis on global gene expression control in Escherichia coli. Nucleic Acids Res. 39, 2073–2091 (2011).
Cho, B. K., Knight, E. M., Barrett, C. L. & Palsson, B. O. Genome-wide analysis of Fis binding in Escherichia coli indicates a causative role for A-/AT-tracts. Genome Res. 18, 900–910 (2008).
Singh, S. S. et al. Widespread suppression of intragenic transcription initiation by H-NS. Genes Dev. 28, 214–219 (2014).
Vora, T., Hottes, A. K. & Tavazoie, S. Protein occupancy landscape of a bacterial genome. Mol. Cell 35, 247–253 (2009). A novel application of genomics to monitor the protein landscape in different parts of a bacterial chromosome, with direct observation of tracts of the genome where transcription is silenced.
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).
The authors were supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC; grant BB/J006076/1) and by the Industrial Biotechnology Catalyst programme (funded by Innovate UK, the BBSRC and the UK Engineering and Physical Sciences Research Council (EPSRC)) to support the translation, development and commercialisation of innovative industrial biotechnology processes.
The authors declare no competing financial interests.
- RNA polymerase core enzyme
The form of bacterial DNA-dependent RNA polymerase that lacks a sigma factor.
- Template strand
The strand of the DNA duplex that acts as a template for RNA synthesis.
- Open complex
The complex between RNA polymerase and a promoter after DNA duplex unwinding has occurred and the RNA polymerase is ready to start transcription.
- Housekeeping sigma factor
The sigma factor in a bacterium that is responsible for the recognition of promoters that control the transcription of most genes.
- Chromatin immunoprecipitation
(ChIP). A method whereby antibodies are used to isolate DNA fragments that have been cross-linked to a specific protein.
- Stationary phase
The period when bacteria have stopped growing.
- Guanosine tetraphosphate
(ppGpp). A small molecule that is synthesized in response to certain stresses. ppGpp is often referred to as 'magic spot', which is a term that also refers to guanosine pentaphosphate (pppGpp).
A class of soil bacteria with a particular morphology.
An extended motif found in proteins.
- Closed complex
The complex between RNA polymerase and a promoter before DNA duplex unwinding has occurred.
- Michaelis constant
The concentration of a substrate at which the reaction catalysed by an enzyme proceeds at half of its maximum speed.
- Initiating nucleotide
The 5′ nucleotide of a transcript.
The structure that forms after a bacterial chromosome is compacted inside a bacterium.
- Superhelical density
The measure of the degree to which the winding of one DNA strand around the other differs from the periodicity of the Watson–Crick structure.
- Enterohaemorrhagic E. coli
A virulent strain of Escherichia coli that causes bloody diarrhoea.
- Pervasive transcription
The synthesis of transcripts that seem not to correspond to any functional genetic unit.
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Browning, D., Busby, S. Local and global regulation of transcription initiation in bacteria. Nat Rev Microbiol 14, 638–650 (2016). https://doi.org/10.1038/nrmicro.2016.103
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