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Journal of Bacteriology, February 2003, p. 1116-1119, Vol. 185, No. 3
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.3.1116-1119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Expression of Primary Sigma Factor (PSF) and PSF-Like Sigma Factors in the Cyanobacterium Synechocystis sp. Strain PCC 6803

Ilona Tuominen, Esa Tyystjärvi, and Taina Tyystjärvi*

Plant Physiology and Molecular Biology, Department of Biology, University of Turku, FIN-20014 Turku, Finland

Received 28 August 2002/ Accepted 13 November 2002


   ABSTRACT
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Large amounts of sigA mRNA, encoding the primary {sigma} factor (PSF) in Synechocystis sp. strain PCC 6803, accumulated under standard growth conditions, while stress conditions like heat or high salinity led to a rapid decrease in sigA mRNA content. The sigB, sigC, sigD, and sigE genes, encoding PSF-like {sigma} factors, were under strict physiological control.


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The initiation of transcription, mediated by RNA polymerase holoenzyme, is the main determinant for gene regulation in eubacteria. The eubacterial RNA polymerase holoenzyme is composed of the core enzyme with the subunit composition of {alpha}2, ß, ß', {omega}, and a {sigma} factor. In cyanobacteria, the ß' subunit is split into two parts and the N-terminal part has been named the {gamma} subunit (21). The core enzyme exhibits the RNA polymerase activity, while the {sigma} factor (3) is responsible for the recognition of a promoter sequence (7). Most bacteria synthesize several {sigma} factors, each of them recognizing a unique set of promoter regions (24). Environmental conditions or developmental signals often cause major changes in gene expression by inducing a swap of {sigma} factors.

Two families of bacterial {sigma} factors ({sigma}70 and {sigma}54) have been identified on the basis of structural and functional similarity (24). The {sigma}70 family is further divided into three subgroups (16). Group 1 is composed of primary {sigma} factors (PSF) that are essential for cell viability and are mainly responsible for the transcription of genes expressed during the exponential-growth phase. Those {sigma} factors that show extensive amino acid similarity to PSF but are not essential for exponential growth belong to group 2 (16). Cyanobacteria, enterobacteria, and the high-GC-content gram-positive bacteria contain many group 2 {sigma} factors (6, 8), but the physiological roles of these numerous PSF-like {sigma} factors are still unclear. Some of the group 2 {sigma} factors might be involved in the adaptation of cyanobacteria to the long-term starvation of nitrogen, carbon, or sulfur (2, 4, 9, 15, 17). Furthermore, in the cyanobacterium Synechococcus elongatus strain PCC 7942, group 2 {sigma} factors affect the settings of the circadian clock (18).

Group 3 consists of {sigma} factors that vary more considerably in amino acid sequence than those of groups 1 or 2. These so-called alternative {sigma} factors are involved in the transcription of specific regulons expressed in extracytoplasmic stress conditions, during sporulation, or in the synthesis of flagella (1, 24).

Nine open reading frames encode putative {sigma} factors in the cyanobacterium Synechocystis sp. strain PCC 6803 (13). All these {sigma} factors belong to the {sigma}70 family. According to sequence homology, the sigA gene encodes the PSF; the sigB, sigC, sigD, and sigE genes encode group 2 {sigma} factors; and the sigF, sigG, sigH, and sigI genes encode group 3 {sigma} factors (6, 13). We started to analyze the possible function of each PSF and PSF-like {sigma} factor by measuring the amount of mRNA produced by these sig genes under environmental conditions known to induce major changes in the physiology of cyanobacteria.

Northern blot analysis. Synechocystis sp. PCC 6803 cells were treated under different environmental conditions, and after the treatments, the cells were harvested and total RNA was isolated (22). Northern blotting was performed using a standard procedure (20). The gene-specific probes were amplified by PCR with the primers indicated in Table 1, and the equal loading of the gels was confirmed by methylene blue staining.


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  		TABLE 1. Primers used to amplify gene-specific probes in Northern blotting

 
sigA encodes the PSF. The sigA gene (slr0653) produced a 1,400-nucleotide (nt)-long full-length transcript and a few shorter ones (Fig. 1). The highest levels of sigA mRNA were detected in exponentially growing cells under standard growth conditions (Fig. 1). Transfer of the cells from light to darkness induced a loss of sigA transcripts (Fig. 1) and cessation of growth of this photosynthetic organism. Similarly, the inhibition of photosystem II (PSII) function in the light by 15 µM 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) treatment induced a gradual loss of sigA transcripts and only 5% of sigA transcripts remained after an 18-h-long DCMU treatment (Fig. 1). Heat shock (42°C) and salt stress (0.5 M NaCl) induced rapid down-regulation of the level of sigA transcripts (Fig. 1). These treatments have been shown to slow down the growth rate of the cells (14). A short cold treatment, in turn, diminished the amount of sigA mRNA only slightly (Fig. 1).



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  		FIG. 1. Amounts of the sigA, sigB, sigC, sigD, and sigE mRNAs under different environmental conditions in Synechocystis sp. PCC 6803. The cells were grown at 32°C in 50 µmol of photons m-2 s-1 (GL) and thereafter either transferred to darkness for 18 h (D) or treated with 15 µM DCMU for 5 min or 18 h, shifted to 42°C for 5 min, treated with 0.5 M NaCl for 15 min, or shifted to 16°C for 10 min. After each treatment, total RNA was isolated and the sigA, sigB, sigC, sigD, and sigE genes were used as probes in Northern hybridizations.

 
The sigA gene produced more transcripts than the other sig genes under growth light conditions, although all sig genes produced at least some transcripts (Fig. 1). This finding, together with the positive correlation between the amount of sigA mRNA and the growth rate of the cells, supports the hypothesis that the sigA gene encodes the PSF in Synechocystis sp. PCC 6803, based on sequence analysis (6).

Many stress conditions induce accumulation of sigB mRNA. The sigB gene (sll0306) produced a 1,350-nt-long transcript (Fig. 1), and some additional shorter RNA species were also detected. Only tiny amounts of sigB transcripts were measured under standard growth conditions, and sigB transcripts totally disappeared after a long dark treatment (Fig. 1). A 5-min heat shock and 15-min high-salt treatment induced a 10-fold increase in sigB transcripts compared to that found under standard growth conditions. Inhibition of PSII function by DCMU treatment rapidly induced a sevenfold increase in the level of sigB transcripts. The enhanced accumulation of sigB transcripts in the presence of DCMU was, however, only transient, as after a long DCMU treatment (18 h), only the same small amount of transcripts as that in the standard growth conditions was present. The amount of sigB mRNA remained at a low level after a short cold treatment (Fig. 1).

Changes in many environmental conditions rapidly induce the transient increase of sigB mRNA (Fig. 1). Interestingly, inactivation of the sigF gene, which encodes an alternative {sigma} factor in Synechocystis sp. PCC 6803, reduces the long-term capacity of the inactivation strain to acclimate to high-salt conditions but does not affect the production of salt stress proteins in the beginning of salt stress (12). Based on those results and on the expression pattern of the sigB gene, we suggest that the acclimation of Synechocystis sp. PCC 6803 to high salinity requires the expression of two different sets of salt stress genes. The first set of genes is recognized by RNA polymerase containing the SigB factor, and, only after a prolonged salt stress, another set of salt stress genes are transcribed using the SigF factor.

Acclimation processes driven by the sequential expression of two different {sigma} factors might be common in cyanobacteria, as also the response to a heat shock apparently requires the function of two different {sigma} factors. Figure 1 shows that transcription of the sigB gene is rapidly activated at the beginning of heat shock but also that slow induction of the sigH gene, encoding an alternative {sigma} factor, occurs during a prolonged high-temperature treatment (12).

sigC, sigD, and sigE are functional genes. The sigC gene (sll0184) produced a 1,000-nt-long transcript (Fig. 1). The amount of sigC transcripts was small in all the conditions tested, although some induction was measured after a short DCMU treatment. In darkness, sigC transcripts were hardly detectable.

The sigE gene (sll1689) produced only very small amounts of transcripts in all the studied conditions (Fig. 1). A slight increase in the 1,250-nt-long sigE transcripts was measured after short DCMU or salt treatment. The sigE transcripts disappeared in darkness (Fig. 1). A long period of nitrogen starvation has been shown to induce, at least to some extent, expression of the sigE gene (rpoD2-V) (17), suggesting that SigE factor might specifically activate transcription of those genes that are required for survival under a low-nitrogen supply. Nitrogen-limiting conditions have been shown to up-regulate the expression of specific group 2 {sigma} factor genes in other cyanobacteria as well (2, 4).

The sigD gene (sll2012) produces a 1,100-nt-long transcript (Fig. 1). Short treatment with DCMU induced an increase in sigD transcripts, whereas the amount sigD mRNA remained at the same level as that in growth conditions after heat, low-temperature, or high-salinity treatments (Fig. 1). The sigD gene was the only sig gene that produced moderate amounts of transcripts in the dark (Fig. 1). Transcription of many genes is down-regulated in the dark, but a few genes, including the cph genes encoding the bacteriophytochromes, are activated in the dark (5, 19).

Light-induced accumulation of sigA mRNA. We next studied in more detail the light regulation of the sigA gene. The loss of sigA transcripts in the dark was rapid, and less than 10% of transcripts remained after a 5-min dark treatment, and after 15 min of darkness, the transcripts were hardly detectable (Fig. 2). In order to study the light activation of transcription of the sigA gene, we first incubated cells overnight in the dark and thereafter followed the activation of transcription under standard growth conditions. After a long dark treatment, some sigA transcripts already accumulated after 5 and 15 min of illumination, but only after 1 h of illumination did the amount of sigA transcripts reach the normal growth light level (Fig. 2). Addition of lincomycin, an inhibitor of translation initiation, totally prevented the accumulation of sigA mRNA after a dark period (Fig. 2), indicating that the light-induced accumulation of the sigA gene requires a de novo-synthesized protein factor.



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  		FIG. 2. Time course of darkness-induced disappearance and light-induced accumulation of sigA and sigB mRNAs in Synechocystis sp. PCC 6803. The cells were first transferred from growth conditions (GL) to darknes,s and the samples were withdrawn after 0-, 5-, 15-, and 60-min- and 18-h dark treatments. After 18-h dark treatment, the cells were shifted back to growth light for 5, 15, and 60 min in the presence or absence of a translation inhibitor, lincomycin (LIN), as indicated. Total RNAs were isolated and the amounts of sigA and sigB mRNAs were analyzed by the Northern blot technique.

 
Similar to sigA transcripts, sigB transcripts disappeared during a long dark treatment. Unlike the sigA transcripts, the sigB transcripts accumulated very rapidly after the onset of illumination (Fig. 2). The largest amount of sigB transcripts was detected already after 5 min of illumination, and after 1 h of illumination, the amount of sigB transcripts was only 10% of that measured after the 5-min illumination (Fig. 2). The rapid light-induced accumulation of sigB mRNA occurred in the presence of a translation inhibitor, lincomycin, indicating that it did not require any newly synthesized protein factor. In the presence of lincomycin, sigB transcripts remained abundant for a longer time after the onset of illumination than in the absence of a protein synthesis inhibitor (Fig. 2). This suggests that a protein factor(s) preventing the accumulation of sigB mRNA is synthesized shortly after the onset of illumination.

The disappearance of the expression peak of sigB mRNA after the onset of illumination parallels the appearance of sigA mRNA, which encodes the PSF. We suggest that the light-induced activation of growth after a dark period might be a two-step procedure. First, only SigB factor is produced, and second, RNA polymerase containing the SigB factor is involved in transcription of the primary SigA factor that recognizes the promoter regions of the housekeeping genes.

In order to identify the photoreceptor involved in the light activation of the sigA gene, we measured the action spectrum of sigA transcripts. Synechocystis sp. PCC 6803 cells were first kept in the dark for 18 h to deplete the sigA transcript pool, and thereafter, the cells were illuminated for 10 min with 50-nm slices of the visible spectrum (23). The photon flux density was 50 µmol m-2 s-1. The largest amount of sigA mRNA was measured in orange light (600 to 650 nm), but even in orange light, the actual level of transcripts remained very low after a 10-min illumination (Fig. 3). Violet, yellow, and red lights were equally efficient in inducing the sigA gene (Fig. 3). Blue light (450 to 500 nm) was very inefficient in inducing transcription of the sigA gene (Fig. 3).



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  		FIG. 3. Action spectra of sigA and psaAB transcription in Synechocystis sp. PCC 6803. (A) Amount of sigA mRNA after 10-min illumination under different light qualities. (B) Amount of psaAB mRNA after 15-min and 1-h illumination under different light qualities. The 5,200-nt-long psaAB mRNA and shorter processed or degraded products of the full-length psaAB mRNA are indicated.

 
The slow activation of sigA transcription after the onset of illumination suggests that the light activation mechanism most probably is more complicated than a direct signaling cascade from a single photoreceptor. It is also apparent that the action spectrum of sigA mRNA does not match with the absorbance spectra of chlorophyll a, phycobilins, carotenoids, bacteriophytochrome, or cryptochrome. Instead, the action spectrum of sigA mRNA (Fig. 3) closely resembles that of photosynthesis (23), indicating that the light activation of the sigA gene follows active photosynthesis. In accordance with this finding, inhibition of photosynthesis with DCMU treatment down-regulates the transcript levels of the sigA gene in the light (Fig. 1).

Our next question was whether the action spectra of housekeeping genes are similar to the action spectrum of the sigA gene, as they should be if SigA is the PSF. The present understanding of the expression of photosynthetic genes encoding the subunits of PSII and PSI (10, 11, 23) allows us to use these psa (PSI) and psb (PSII) genes as models of housekeeping genes. These genes produce the photosynthetic machinery for the daughter cells during the exponential-growth phase. Only the psbA2 and psbD2 genes, encoding the PSII reaction center proteins D1 and D2, respectively, cannot be considered to be such housekeeping genes because psbA (and psbD2) transcripts are mainly required for the repair of the photodamaged PSII centers (10, 23).

To measure the action spectrum of psaAB transcripts, the cells were first dark treated for 18 h and thereafter illuminated with 50-nm slices of the visible spectrum for 15 min or 1 h. The psaAB transcripts appeared in Northern blots as many separate RNA bands. The psaAB operon was transcribed as a 5,200-nt-long dicistronic transcript, and later, this full-length transcript was processed or degraded to shorter species (11). The longest-processed products may contain either full-length psaA or psaB transcript. The processed products of psaAB transcripts are very stable in the dark (11) and can be detected even after 18 h of dark treatment. The action spectrum of the psaAB operon was very similar to that of the sigA gene, showing the largest amount of newly synthesized 5,200-nt-long psaAB mRNA after treatment under orange light and almost no psaAB mRNA in blue light (Fig. 3). Red, yellow, and violet light induced transcription of the psaAB operon almost as efficiently as orange light. A similar action spectrum has been measured for the psbDC operon previously (23). Although the action spectra of the psaAB and psbDC operons and that of the sigA gene closely resemble each other, the time scale of gene activation was different. Small amounts of sigA mRNA were measured already after 10 min of illumination, but 15 min of illumination was too short to induce transcription of the psaAB operon.

Transcription of many psa and psb genes is rapidly inactivated in the dark (10, 11) simultaneously with the disappearance of sigA mRNA. Furthermore, onset of illumination after the long dark treatment induces the transcription of many psa and psb genes very slowly (only traces of transcripts after 1 h of illumination) and requires a de novo-synthesized protein factor (10, 11). Our results indicate that the light activation of transcription of these psa and psb genes occurs more slowly than photoactivation of the sigA gene (Fig. 3). Thus, we suggest that SigA factor is actually the de novo-synthesized protein factor that is required for light-induced activation of the transcription of the psa and psb genes.


   ACKNOWLEDGMENTS
 
This work was supported by the Academy of Finland.

Paula Mulo is warmly thanked for the critical reading of the manuscript.


   FOOTNOTES
 
* Corresponding author. Mailing address: Plant Physiology and Molecular Biology, Department of Biology, University of Turku, FIN-20014 Turku, Finland. Phone: 358-2-3338078. Fax: 358-2-3338075. E-mail: taityy{at}utu.fi. Back


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Journal of Bacteriology, February 2003, p. 1116-1119, Vol. 185, No. 3
0021-9193/03/$08.00+0     DOI: 10.1128/JB.185.3.1116-1119.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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