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  • Review Article
  • Published:

Advances in bacterial promoter recognition and its control by factors that do not bind DNA

Nature Reviews Microbiology volume 6, pages 507–519 (2008)Cite this article

Key Points

  • Promoter recognition in bacteria is a more complex process than originally recognized, directly involving at least five separable RNA-polymerase binding elements in the promoter and at least five promoter-binding domains or subdomains in RNA polymerase.

  • The five RNA polymerase recognition elements in bacterial promoters are the UP element that is bound by the carboxy-terminal domains of the two α subunits, the −35 element that is bound by σ region 4.2, the extended −10 element that is bound by σ region 3.0, the −10 element that is bound by σ regions 2.3 and 2.4 and the discriminator element that is bound by σ region 1.2.

  • Transcription initiation is a multistep process in which the interactions between RNA polymerase and the promoter determine the precise kinetics of the reaction. DNA-sequence variation among promoters in each of the RNA polymerase recognition elements leads to variation in the microscopic rate constants that result in the unique kinetic properties of individual promoters.

  • Regulators of transcription initiation that bind to RNA polymerase without binding to DNA include: the concentration of the first NTP in the transcript, the unusual nucleotide ppGpp, 6S RNA, anti-σ factors and the small protein DksA. In addition, the σ-factor binding protein Crl seems to increase the rate of holoenzyme assembly.

  • Regulators of transcription that bind to RNA polymerase without binding to DNA are able to achieve promoter-specific regulation by targeting steps in the mechanism that are rate limiting for subsets of promoters.

  • Each of these regulators can achieve global changes in the transcription profile of the cell.

Abstract

Early work identified two promoter regions, the −10 and −35 elements, that interact sequence specifically with bacterial RNA polymerase (RNAP). However, we now know that several additional promoter elements contact RNAP and influence transcription initiation. Furthermore, our picture of promoter control has evolved beyond one in which regulation results solely from activators and repressors that bind to DNA sequences near the RNAP binding site: many important transcription factors bind directly to RNAP without binding to DNA. These factors can target promoters by affecting specific kinetic steps on the pathway to open complex formation, thereby regulating RNA output from specific promoters.

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Figure 1: DNA elements and RNAP modules that contribute to promoter recognition by Eσ70.
Figure 2: Models of the open complex.
Figure 3: Steps in transcription initiation.

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Acknowledgements

We thank colleagues in our laboratory and other laboratories who provided valuable input on sections of the text and figures, including C. Turnbough, R. Landick, R. Ebright, A. Hochschild and T. Record, and apologize to those investigators whose work has not been cited owing to space limitations. Our work is supported by the National Institutes of Health (grant R37 GM37048).

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  1. Department of Bacteriology, University of Wisconsin– Madison, 1550 Linden Drive, Madison, 53706, Wisconsin, USA

    Shanil P. Haugen, Wilma Ross & Richard L. Gourse

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Glossary

Template strand

The strand of DNA that enters the active site of RNA polymerase and is used as a guide for RNA synthesis. +1 is defined as the position where the template strand pairs with the nucleoside 5′-triphosphate that forms the 5′ end of the transcript. The RNA transcript is the reverse complement of the template strand and has the same sequence as the non-template strand.

Footprinting

A biochemical assay for detecting protein binding sites on DNA. A protein is allowed to bind to end-labelled DNA, the DNA is subjected to limited enzymatic or chemical nuclease cleavage and DNA fragments are separated by polyacrylamide electrophoresis under conditions that allow single-nucleotide resolution.

Crosslinking

A biochemical technique for identifying interactions between macromolecules. Typically, covalent bonds between macromolecules are induced by ultraviolet or chemical exposure.

Promoter clearance

The step in transcription in which RNAP breaks its interactions with the promoter and begins productive RNA synthesis.

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Haugen, S., Ross, W. & Gourse, R. Advances in bacterial promoter recognition and its control by factors that do not bind DNA. Nat Rev Microbiol 6, 507–519 (2008). https://doi.org/10.1038/nrmicro1912

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