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J Bacteriol. 2016 October 1; 198(19): 2550.
Published online 2016 September 9. doi:  10.1128/JB.00576-16
PMCID: PMC5019068

Classic Spotlight: the Heat Shock Response and the Discovery of Alternative Sigma Factors in Escherichia coli


In the late 1970s and early 1980s, Takashi Yura in Japan, Fred Neidhardt in the United States, and their colleagues investigated the origins of the so-called heat shock response in Escherichia coli. These studies ultimately resulted in the identification of the alternative sigma factor sigma 32. Many of the early reports (e.g., references 1, 2, 3, and 4), as well as reports on other sigma factors from E. coli and from other bacterial species and bacteriophages, were published in the Journal of Bacteriology.

As had been shown in eukaryotes many years before, the heat shock response is a transient, virtually universal response in which specific gene products are induced by increases in temperature or by other environmental stresses. We now know that many of these gene products are chaperones or related proteins that are needed to address protein folding problems. The Yura and Neidhardt groups showed that a gene called htpR is required for this response in E. coli (4, 5). The htpR gene was sequenced by Landick and colleagues (6), and from the similarity of the predicted protein product to the major E. coli sigma factor, sigma 70, it was predicted that HtpR might be a sigma factor. Alan Grossman, James Erickson, and Carol Gross then showed that the RNA polymerase holoenzyme reconstituted from the core enzyme and HtpR is necessary and sufficient for transcription from heat shock promoters in vitro (7). Two decades of work from the Gross lab and other labs worked out the identity of the regulon controlled by HtpR (which was renamed sigma 32), as well as the mechanism by which modulation of the synthesis, degradation, and activity of sigma 32 regulates the heat shock response (which is now often referred to as the unfolded protein response).

The discovery of alternative sigma factors in another bacterial species, Bacillus subtilis, by Jan Pero, Richard Losick, and Michael Chamberlin, reviewed in reference 8, actually predated by several years the identification of sigma 32 as an alternative sigma factor in E. coli. Their work demonstrated that B. subtilis and some of its phages use alternative sigma factors to reprogram RNA polymerase to recognize specific promoters and control changes in gene expression. By the early 1990s, extensive characterization of sigma 32 and the other five alternative E. coli sigma factors, as well as the sigma factors encoded by B. subtilis and many other bacteria and phages (summarized in reference 9), had established that the utilization of alternative sigma factors is a major mechanism for regulation of gene expression and development in bacteria.


The views expressed in this Editorial do not necessarily reflect the views of the journal or of ASM.


1. Yamamori T, Ito K, Nakamura Y, Yura T 1978. Transient regulation of protein synthesis in Escherichia coli upon shift-up of growth temperature. J Bacteriol 134:1133–1140. [PMC free article] [PubMed]
2. Herendeen SL, VanBogelen RA, Neidhardt FC 1979. Levels of major proteins of Escherichia coli during growth at different temperatures. J Bacteriol 139:185–194. [PMC free article] [PubMed]
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5. Yura T, Tobe T, Ito K, Osawa T 1984. Heat shock regulatory gene (htpR) of Escherichia coli is required for growth at high temperature but is dispensable at low temperature. Proc Natl Acad Sci U S A 81:6803–6807. doi:.10.1073/pnas.81.21.6803 [PubMed] [Cross Ref]
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7. Grossman AD, Erickson JW, Gross CA 1984. The htpR gene product of E. coli is a sigma factor for heat-shock promoters. Cell 38:383–390. doi:.10.1016/0092-8674(84)90493-8 [PubMed] [Cross Ref]
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