Sigma Factors in Gene Expression

Abstract

Sigma (σ) factors control the promoter selectivity of bacterial RNA polymerase (RNAP). On binding to RNAP, σ factors allow efficient promoter recognition and transcription initiation. Bacterial promoters are typically comprised of two hexameric deoxyribonucleic acid (DNA) sequences located approximately 10 and 35 bases upstream of the transcription start site (the −10 and −35 element, respectively). All bacteria contain a primary σ factor that is responsible for transcription of housekeeping genes necessary for growth and survival. In addition, many bacteria encode multiple alternative σ factors. The level and activity of the alternative σ factors are highly regulated and can vary depending on environmental or developmental signals. The synthesis of alternative σ factors allows the coordinated activation of discrete sets of genes through the recognition of distinct promoter sequences and thereby contributes to stress responses, motility, endospore formation and numerous other adaptive responses.

Key Concepts:

  • σ Factors are necessary for promoter recognition by RNA polymerase and efficient transcription initiation.

  • Transcription initiation is a highly regulated, multistep process.

  • σ Factors can be grouped into two families on the basis of their similarity to the housekeeping σ factor, σ70, or the nitrogen‐responsive σ factor, σ54.

  • Members of the σ70 family generally contain four conserved domains (regions 1–4).

  • Most bacteria encode multiple alternative σ factors that direct transcription of genes in response to environmental cues and developmental transitions. Alternative σ70 family proteins often lack region 1 and sometimes region 3 (minimally containing conserved regions 2 and 4).

  • σ Factor activity can be regulated at many levels, such as through sequestration by anti‐σ factors or by protolytic activation.

Keywords: sigma; RNA polymerase; transcription; promoter; regulation

Figure 1.

Generic structure–function map for members of the σ70 family. The protein sequence is represented as a bar from the N‐terminus (left) to the C‐terminus (right). The amino acid sequence is divided into four conserved regions. Regions 2 and 4 (blue) contain the key regions implicated in core binding and promoter recognition and melting. Recognition of the −35 promoter element is mediated by a helix–turn–helix (HTH) unit in region 4 and amino acids from this region may also provide a contact point for some activator proteins. Amino acids important for both −10 region recognition and promoter melting are on an α helix (helix 14) spanning regions 2.3 and 2.4.

Figure 2.

A close‐up view of interactions between E. coli σ70 and a consensus promoter element. The σ factor has two domains corresponding roughly to regions 2 and 4. Region 2 interacts with the −10 element. Conserved threonine (T) and glutamine (Q) residues are implicated in recognition of the start site distal thymine (T in the DNA). An adjacent cluster of aromatic amino acid side chains (two tryptophan, W, and a tyrosine, Y) provides hydrophobic and stacking interactions (stippled bars) with the ssDNA formed during melting of the promoter DNA. Recognition of the −35 element by region 4 involves, in part, specific amino acid side chain contacts from two arginine (R) residues with the edges of the base pairs.

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Chandrangsu, Pete, and Helmann, John D(Mar 2014) Sigma Factors in Gene Expression. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000854.pub3]