The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally

English version České info

Despite the importance of maintaining redox homeostasis for cellular viability, how cells control redox balance globally is poorly understood. Here we provide new mechanistic insight into how the balance between reduced and oxidized electron carriers is regulated at the level of gene expression by mapping the regulon of the response regulator ArcA from Escherichia coli, which responds to the quinone/quinol redox couple via its membrane-bound sensor kinase, ArcB. Our genome-wide analysis reveals that ArcA reprograms metabolism under anaerobic conditions such that carbon oxidation pathways that recycle redox carriers via respiration are transcriptionally repressed by ArcA. We propose that this strategy favors use of catabolic pathways that recycle redox carriers via fermentation akin to lactate production in mammalian cells. Unexpectedly, bioinformatic analysis of the sequences bound by ArcA in ChIP-seq revealed that most ArcA binding sites contain additional direct repeat elements beyond the two required for binding an ArcA dimer. DNase I footprinting assays suggest that non-canonical arrangements of cis-regulatory modules dictate both the length and concentration-sensitive occupancy of DNA sites. We propose that this plasticity in ArcA binding site architecture provides both an efficient means of encoding binding sites for ArcA, σ⁷⁰-RNAP and perhaps other transcription factors within the same narrow sequence space and an effective mechanism for global control of carbon metabolism to maintain redox homeostasis.

Vyšlo v časopise: The Bacterial Response Regulator ArcA Uses a Diverse Binding Site Architecture to Regulate Carbon Oxidation Globally. PLoS Genet 9(10): e32767. doi:10.1371/journal.pgen.1003839
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003839

Souhrn

Zdroje

1. PackerL, CadenasE (2011) Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr 48: 26–32.

2. van HoekMJ, MerksRM (2012) Redox balance is key to explaining full vs. partial switching to low-yield metabolism. BMC Syst Biol 6: 22.

3. KornasA, KuzniakE, SlesakI, MiszalskiZ (2010) The key role of the redox status in regulation of metabolism in photosynthesizing organisms. Acta Biochim Pol 57: 143–151.

4. TrachoothamD, LuW, OgasawaraMA, NilsaRD, HuangP (2008) Redox regulation of cell survival. Antioxid Redox Signal 10: 1343–1374.

5. BergerF, Ramirez-HernandezMH, ZieglerM (2004) The new life of a centenarian: signalling functions of NAD(P). Trends Biochem Sci 29: 111–118.

6. BrekasisD, PagetMS (2003) A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2). EMBO J 22: 4856–4865.

7. AbateC, PatelL, RauscherFJ (1990) Redox regulation of fos and jun DNA-binding activity in vitro. Science 249: 1157–1161.

8. DanonA, MayfieldSP (1994) Light-regulated translation of chloroplast messenger RNAs through redox potential. Science 266: 1717–1719.

9. HaddadJJ (2004) Oxygen sensing and oxidant/redox-related pathways. Biochem Biophys Res Commun 316: 969–977.

10. SchaferFQ, BuettnerGR (2001) Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 30: 1191–1212.

11. ZhangQ, PistonDW, GoodmanRH (2002) Regulation of corepressor function by nuclear NADH. Science 295: 1895–1897.

12. RutterJ, ReickM, WuLC, McKnightSL (2001) Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293: 510–514.

13. SnoepJL, de GraefMR, WestphalAH, de KokA, Teixeira de MattosMJ, et al. (1993) Differences in sensitivity to NADH of purified pyruvate dehydrogenase complexes of Enterococcus faecalis, Lactococcus lactis, Azotobacter vinelandii and Escherichia coli: implications for their activity in vivo. FEMS Microbiol Lett 114: 279–283.

14. LeonardoMR, DaillyY, ClarkDP (1996) Role of NAD in regulating the adhE gene of Escherichia coli. J Bacteriol 178: 6013–6018.

15. AlvarezAF, GeorgellisD (2010) In vitro and in vivo analysis of the ArcB/A redox signaling pathway. Methods Enzymol 471: 205–228.

16. RolfeMD, Ter BeekA, GrahamAI, TrotterEW, AsifHM, et al. (2011) Transcript profiling and inference of Escherichia coli K-12 ArcA activity across the range of physiologically relevant oxygen concentrations. J Biol Chem 286: 10147–10154.

17. IuchiS, LinEC (1992) Purification and phosphorylation of the Arc regulatory components of Escherichia coli. J Bacteriol 174: 5617–5623.

18. GeorgellisD, KwonO, LinEC (2001) Quinones as the redox signal for the Arc two-component system of bacteria. Science 292: 2314–2316.

19. MalpicaR, FrancoB, RodriguezC, KwonO, GeorgellisD (2004) Identification of a quinone-sensitive redox switch in the ArcB sensor kinase. Proc Natl Acad Sci U S A 101: 13318–13323.

20. BekkerM, AlexeevaS, LaanW, SawersG, Teixeira de MattosJ, et al. (2010) The ArcBA two-component system of Escherichia coli is regulated by the redox state of both the ubiquinone and the menaquinone pool. J Bacteriol 192: 746–754.

21. GeorgellisD, KwonO, LinEC (1999) Amplification of signaling activity of the Arc two-component system of Escherichia coli by anaerobic metabolites. An in vitro study with different protein modules. J Biol Chem 274: 35950–35954.

22. HolmAK, BlankLM, OldigesM, SchmidA, SolemC, et al. (2010) Metabolic and transcriptional response to cofactor perturbations in Escherichia coli. J Biol Chem 285: 17498–17506.

23. ChaoG, ShenJ, TsengCP, ParkSJ, GunsalusRP (1997) Aerobic regulation of isocitrate dehydrogenase gene (icd) expression in Escherichia coli by the arcA and fnr gene products. J Bacteriol 179: 4299–4304.

24. LynchAS, LinEC (1996) Transcriptional control mediated by the ArcA two-component response regulator protein of Escherichia coli: characterization of DNA binding at target promoters. J Bacteriol 178: 6238–6249.

25. ChoBK, KnightEM, PalssonBO (2006) Transcriptional regulation of the fad regulon genes of Escherichia coli by ArcA. Microbiology 152: 2207–2219.

26. CunninghamL, GeorgellisD, GreenJ, GuestJR (1998) Co-regulation of lipoamide dehydrogenase and 2-oxoglutarate dehydrogenase synthesis in Escherichia coli: characterization of an ArcA binding site in the lpd promoter. FEMS Microbiol Lett 169: 403–408.

27. ShenJ, GunsalusRP (1997) Role of multiple ArcA recognition sites in anaerobic regulation of succinate dehydrogenase (sdhCDAB) gene expression in Escherichia coli. Mol Microbiol 26: 223–236.

28. PellicerMT, LynchAS, De WulfP, BoydD, AguilarJ, et al. (1999) A mutational study of the ArcA-P binding sequences in the aldA promoter of Escherichia coli. Mol Gen Genet 261: 170–176.

29. PellicerMT, FernandezC, BadiaJ, AguilarJ, LinEC, et al. (1999) Cross-induction of glc and ace operons of Escherichia coli attributable to pathway intersection. Characterization of the glc promoter. J Biol Chem 274: 1745–1752.

30. DrapalN, SawersG (1995) Purification of ArcA and analysis of its specific interaction with the pfl promoter-regulatory region. Mol Microbiol 16: 597–607.

31. NesbitAD, FleischhackerAS, TeterSJ, KileyPJ (2012) ArcA and AppY antagonize IscR repression of hydrogenase-1 expression under anaerobic conditions, revealing a novel mode of O2 regulation of gene expression in Escherichia coli. J Bacteriol 194: 6892–6899.

32. LiuX, De WulfP (2004) Probing the ArcA-P modulon of Escherichia coli by whole genome transcriptional analysis and sequence recognition profiling. J Biol Chem 279: 12588–12597.

33. SalmonKA, HungSP, SteffenNR, KruppR, BaldiP, et al. (2005) Global gene expression profiling in Escherichia coli K12: effects of oxygen availability and ArcA. J Biol Chem 280: 15084–15096.

34. GerasimovaAVGM, MakeevVY, MironovAAaFA (2003) ArcA regulator of Gamma-Proteobacteria- Identification of the Binding Signal and Description of the Regulon. Biophysics 48: S21–S25.

35. WangX, GaoH, ShenY, WeinstockGM, ZhouJ, et al. (2008) A high-throughput percentage-of-binding strategy to measure binding energies in DNA-protein interactions: application to genome-scale site discovery. Nucleic Acids Res 36: 4863–4871.

36. OgasawaraH, TeramotoJ, YamamotoS, HiraoK, YamamotoK, et al. (2005) Negative regulation of DNA repair gene (uvrA) expression by ArcA/ArcB two-component system in Escherichia coli. FEMS Microbiol Lett 251: 243–249.

37. LeeYS, HanJS, JeonY, HwangDS (2001) The Arc two-component signal transduction system inhibits in vitro Escherichia coli chromosomal initiation. J Biol Chem 276: 9917–9923.

38. JeongJY, KimYJ, ChoN, ShinD, NamTW, et al. (2004) Expression of ptsG encoding the major glucose transporter is regulated by ArcA in Escherichia coli. J Biol Chem 279: 38513–38518.

39. MikaF, HenggeR (2005) A two-component phosphotransfer network involving ArcB, ArcA, and RssB coordinates synthesis and proteolysis of sigmaS (RpoS) in E. coli. Genes Dev 19: 2770–2781.

40. TardatB, TouatiD (1993) Iron and oxygen regulation of Escherichia coli MnSOD expression: competition between the global regulators Fur and ArcA for binding to DNA. Mol Microbiol 9: 53–63.

41. LunDS, SherridA, WeinerB, ShermanDR, GalaganJE (2009) A blind deconvolution approach to high-resolution mapping of transcription factor binding sites from ChIP-seq data. Genome Biol 10: R142.

42. BaileyTL, ElkanC (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2: 28–36.

43. GaoR, StockAM (2009) Biological insights from structures of two-component proteins. Annu Rev Microbiol 63: 133–154.

44. GrimaudR, EzratyB, MitchellJK, LafitteD, BriandC, et al. (2001) Repair of oxidized proteins. Identification of a new methionine sulfoxide reductase. J Biol Chem 276: 48915–48920.

45. RitzD, PatelH, DoanB, ZhengM, AslundF, et al. (2000) Thioredoxin 2 is involved in the oxidative stress response in Escherichia coli. J Biol Chem 275: 2505–2512.

46. O'HandleySF, FrickDN, DunnCA, BessmanMJ (1998) Orf186 represents a new member of the Nudix hydrolases, active on adenosine(5′)triphospho(5′)adenosine, ADP-ribose, and NADH. J Biol Chem 273: 3192–3197.

47. KeselerIM, Collado-VidesJ, Santos-ZavaletaA, Peralta-GilM, Gama-CastroS, et al. (2011) EcoCyc: a comprehensive database of Escherichia coli biology. Nucleic Acids Res 39: D583–590.

48. MuirM, WilliamsL, FerenciT (1985) Influence of transport energization on the growth yield of Escherichia coli. J Bacteriol 163: 1237–1242.

49. MyersKS, YanH, OngIM, ChungD, LiangK, et al. (2013) Genome-scale Analysis of Escherichia coli FNR Reveals Complex Features of Transcription Factor Binding. PLoS Genet 9: e1003565.

50. KimD, HongJS, QiuY, NagarajanH, SeoJH, et al. (2012) Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling. PLoS Genet 8: e1002867.

51. VolbedaA, DarnaultC, ParkinA, SargentF, ArmstrongFA, et al. (2013) Crystal structure of the O(2)-tolerant membrane-bound hydrogenase 1 from Escherichia coli in complex with its cognate cytochrome b. Structure 21: 184–190.

52. AtlungT, BrondstedL (1994) Role of the transcriptional activator AppY in regulation of the cyx appA operon of Escherichia coli by anaerobiosis, phosphate starvation, and growth phase. J Bacteriol 176: 5414–5422.

53. MaZ, GongS, RichardH, TuckerDL, ConwayT, et al. (2003) GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12. Mol Microbiol 49: 1309–1320.

54. TramontiA, ViscaP, De CanioM, FalconiM, De BiaseD (2002) Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system. J Bacteriol 184: 2603–2613.

55. GongS, RichardH, FosterJW (2003) YjdE (AdiC) is the arginine:agmatine antiporter essential for arginine-dependent acid resistance in Escherichia coli. J Bacteriol 185: 4402–4409.

56. MatesAK, SayedAK, FosterJW (2007) Products of the Escherichia coli acid fitness island attenuate metabolite stress at extremely low pH and mediate a cell density-dependent acid resistance. J Bacteriol 189: 2759–2768.

57. DurandS, StorzG (2010) Reprogramming of anaerobic metabolism by the FnrS small RNA. Mol Microbiol 75: 1215–1231.

58. BoysenA, Moller-JensenJ, KallipolitisB, Valentin-HansenP, OvergaardM (2010) Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli. J Biol Chem 285: 10690–10702.

59. MakinoK, AmemuraM, KawamotoT, KimuraS, ShinagawaH, et al. (1996) DNA binding of PhoB and its interaction with RNA polymerase. J Mol Biol 259: 15–26.

60. PrattLA, SilhavyTJ (1994) OmpR mutants specifically defective for transcriptional activation. J Mol Biol 243: 579–594.

61. SlauchJM, RussoFD, SilhavyTJ (1991) Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the alpha subunit of RNA polymerase. J Bacteriol 173: 7501–7510.

62. CotterPA, MelvilleSB, AlbrechtJA, GunsalusRP (1997) Aerobic regulation of cytochrome d oxidase (cydAB) operon expression in Escherichia coli: roles of Fnr and ArcA in repression and activation. Mol Microbiol 25: 605–615.

63. FerrandezA, GarciaJL, DiazE (2000) Transcriptional regulation of the divergent paa catabolic operons for phenylacetic acid degradation in Escherichia coli. J Biol Chem 275: 12214–12222.

64. PapenfortK, SaidN, WelsinkT, LucchiniS, HintonJC, et al. (2009) Specific and pleiotropic patterns of mRNA regulation by ArcZ, a conserved, Hfq-dependent small RNA. Mol Microbiol 74: 139–158.

65. MandinP, GottesmanS (2010) Integrating anaerobic/aerobic sensing and the general stress response through the ArcZ small RNA. EMBO J 29: 3094–3107.

66. AlexeevaS, HellingwerfKJ, Teixeira de MattosMJ (2003) Requirement of ArcA for redox regulation in Escherichia coli under microaerobic but not anaerobic or aerobic conditions. J Bacteriol 185: 204–209.

67. LevanonSS, SanKY, BennettGN (2005) Effect of oxygen on the Escherichia coli ArcA and FNR regulation systems and metabolic responses. Biotechnol Bioeng 89: 556–564.

68. EvansMR, FinkRC, Vazquez-TorresA, PorwollikS, Jones-CarsonJ, et al. (2011) Analysis of the ArcA regulon in anaerobically grown Salmonella entericasv. Typhimurium. BMC Microbiol 11: 58.

69. IuchiS, AristarkhovA, DongJM, TaylorJS, LinEC (1994) Effects of nitrate respiration on expression of the Arc-controlled operons encoding succinate dehydrogenase and flavin-linked L-lactate dehydrogenase. J Bacteriol 176: 1695–1701.

70. BidartGN, RuizJA, de AlmeidaA, MendezBS, NikelPI (2012) Manipulation of the anoxic metabolism in Escherichia coli by ArcB deletion variants in the ArcBA two-component system. Appl Environ Microbiol 78: 8784–8794.

71. MatsubaraM, KitaokaSI, TakedaSI, MizunoT (2000) Tuning of the porin expression under anaerobic growth conditions by his-to-Asp cross-phosphorelay through both the EnvZ-osmosensor and ArcB-anaerosensor in Escherichia coli. Genes Cells 5: 555–569.

72. NystromT, LarssonC, GustafssonL (1996) Bacterial defense against aging: role of the Escherichia coli ArcA regulator in gene expression, readjusted energy flux and survival during stasis. EMBO J 15: 3219–3228.

73. JonesSA, ChowdhuryFZ, FabichAJ, AndersonA, SchreinerDM, et al. (2007) Respiration of Escherichia coli in the mouse intestine. Infect Immun 75: 4891–4899.

74. GovantesF, OrjaloAV, GunsalusRP (2000) Interplay between three global regulatory proteins mediates oxygen regulation of the Escherichia coli cytochrome d oxidase (cydAB) operon. Mol Microbiol 38: 1061–1073.

75. AtlungT, SundS, OlesenK, BrondstedL (1996) The histone-like protein H-NS acts as a transcriptional repressor for expression of the anaerobic and growth phase activator AppY of Escherichia coli. J Bacteriol 178: 3418–3425.

76. WybornNR, MessengerSL, HendersonRA, SawersG, RobertsRE, et al. (2002) Expression of the Escherichia coli yfiD gene responds to intracellular pH and reduces the accumulation of acidic metabolic end products. Microbiology 148: 1015–1026.

77. SirkoA, ZeheleinE, FreundlichM, SawersG (1993) Integration host factor is required for anaerobic pyruvate induction of pfl operon expression in Escherichia coli. J Bacteriol 175: 5769–5777.

78. StrohmaierH, NoigesR, KotschanS, SawersG, HogenauerG, et al. (1998) Signal transduction and bacterial conjugation: characterization of the role of ArcA in regulating conjugative transfer of the resistance plasmid R1. J Mol Biol 277: 309–316.

79. RolfeMD, OconeA, StapletonMR, HallS, TrotterEW, et al. (2012) Systems analysis of transcription factor activities in environments with stable and dynamic oxygen concentrations. Open Biol 2: 120091.

80. YoshidaT, QinL, EggerLA, InouyeM (2006) Transcription regulation of ompF and ompC by a single transcription factor, OmpR. J Biol Chem 281: 17114–17123.

81. KimSK, KimuraS, ShinagawaH, NakataA, LeeKS, et al. (2000) Dual transcriptional regulation of the Escherichia coli phosphate-starvation-inducible psiE gene of the phosphate regulon by PhoB and the cyclic AMP (cAMP)-cAMP receptor protein complex. J Bacteriol 182: 5596–5599.

82. KasaharaM, MakinoK, AmemuraM, NakataA, ShinagawaH (1991) Dual regulation of the ugp operon by phosphate and carbon starvation at two interspaced promoters. J Bacteriol 173: 549–558.

83. YangC, HuangTW, WenSY, ChangCY, TsaiSF, et al. (2012) Genome-wide PhoB binding and gene expression profiles reveal the hierarchical gene regulatory network of phosphate starvation in Escherichia coli. PLoS One 7: e47314.

84. PerkinsTT, DaviesMR, KlemmEJ, RowleyG, WilemanT, et al. (2013) ChIP-seq and transcriptome analysis of the OmpR regulon of Salmonella enterica serovars Typhi and Typhimurium reveals accessory genes implicated in host colonization. Mol Microbiol 87: 526–538.

85. GriffithKL, GrossmanAD (2008) A degenerate tripartite DNA-binding site required for activation of ComA-dependent quorum response gene expression in Bacillus subtilis. J Mol Biol 381: 261–275.

86. KimSK, MakinoK, AmemuraM, ShinagawaH, NakataA (1993) Molecular analysis of the phoH gene, belonging to the phosphate regulon in Escherichia coli. J Bacteriol 175: 1316–1324.

87. NeidhardtFC, BlochPL, SmithDF (1974) Culture medium for enterobacteria. J Bacteriol 119: 736–747.

88. KangY, WeberKD, QiuY, KileyPJ, BlattnerFR (2005) Genome-wide expression analysis indicates that FNR of Escherichia coli K-12 regulates a large number of genes of unknown function. J Bacteriol 187: 1135–1160.

89. Miller JH (1972) Experiments in molecular genetics. [Cold Spring Harbor, N.Y.]: Cold Spring Harbor Laboratory.

90. DavisSE, MooneyRA, KaninEI, GrassJ, LandickR, et al. (2011) Mapping E. coli RNA polymerase and associated transcription factors and identifying promoters genome-wide. Methods Enzymol 498: 449–471.

91. HuberW, von HeydebreckA, SultmannH, PoustkaA, VingronM (2002) Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18 Suppl 1: S96–104.

92. DufourYS, LandickR, DonohueTJ (2008) Organization and evolution of the biological response to singlet oxygen stress. J Mol Biol 383: 713–730.

93. BiedaM, XuX, SingerMA, GreenR, FarnhamPJ (2006) Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome. Genome Res 16: 595–605.

94. HomannOR, JohnsonAD (2010) MochiView: versatile software for genome browsing and DNA motif analysis. BMC Biol 8: 49.

95. LiR, YuC, LiY, LamTW, YiuSM, et al. (2009) SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25: 1966–1967.

96. ValouevA, JohnsonDS, SundquistA, MedinaC, AntonE, et al. (2008) Genome-wide analysis of transcription factor binding sites based on ChIP-Seq data. Nat Methods 5: 829–834.

97. SchneiderTD (1997) Information content of individual genetic sequences. J Theor Biol 189: 427–441.

98. BlattnerFR, PlunkettG (1997) The complete genome sequence of Escherichia coli K-12. Science 277: 1453–1462.

99. BlancoAG, SolaM, Gomis-RuthFX, CollM (2002) Tandem DNA recognition by PhoB, a two-component signal transduction transcriptional activator. Structure 10: 701–713.

100. SchneiderTD (1997) Sequence walkers: a graphical method to display how binding proteins interact with DNA or RNA sequences. Nucleic Acids Res 25: 4408–4415.

101. DatsenkoKA, WannerBL (2000) One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97: 6640–6645.

102. KhodurskyAB, BernsteinJA, PeterBJ, RhodiusV, WendischVF, et al. (2003) Escherichia coli spotted double-strand DNA microarrays: RNA extraction, labeling, hybridization, quality control, and data management. Methods Mol Biol 224: 61–78.

103. BolstadBM, IrizarryRA, AstrandM, SpeedTP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185–193.

104. SchwalbachMS, KeatingDH, TremaineM, MarnerWD, ZhangY, et al. (2012) Complex physiology and compound stress responses during fermentation of alkali-pretreated corn stover hydrolysate by an Escherichia coli ethanologen. Appl Environ Microbiol 78: 3442–3457.

105. BeattyCM, BrowningDF, BusbySJ, WolfeAJ (2003) Cyclic AMP receptor protein-dependent activation of the Escherichia coli acs P2 promoter by a synergistic class III mechanism. J Bacteriol 185: 5148–5157.

106. FerrandezA, MinambresB, GarciaB, OliveraER, LuengoJM, et al. (1998) Catabolism of phenylacetic acid in Escherichia coli. Characterization of a new aerobic hybrid pathway. J Biol Chem 273: 25974–25986.

107. FraleyCD, KimJH, McCannMP, MatinA (1998) The Escherichia coli starvation gene cstC is involved in amino acid catabolism. J Bacteriol 180: 4287–4290.

108. NakaoT, YamatoI, AnrakuY (1987) Nucleotide sequence of putC, the regulatory region for the put regulon of Escherichia coli K12. Mol Gen Genet 210: 364–368.

109. DaviesSJ, GolbyP, OmraniD, BroadSA, HarringtonVL, et al. (1999) Inactivation and regulation of the aerobic C(4)-dicarboxylate transport (dctA) gene of Escherichia coli. J Bacteriol 181: 5624–5635.

110. ProstJF, NegreD, OudotC, MurakamiK, IshihamaA, et al. (1999) Cra-dependent transcriptional activation of the icd gene of Escherichia coli. J Bacteriol 181: 893–898.

111. NesbitAD, GielJL, RoseJC, KileyPJ (2009) Sequence-specific binding to a subset of IscR-regulated promoters does not require IscR Fe-S cluster ligation. J Mol Biol 387: 28–41.

112. MaxamAM, GilbertW (1980) Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol 65: 499–560.

113. SchneiderTD, StephensRM (1990) Sequence logos: a new way to display consensus sequences. Nucleic Acids Res 18: 6097–6100.

114. NeuwegerH, PersickeM, AlbaumSP, BekelT, DondrupM, et al. (2009) Visualizing post genomics data-sets on customized pathway maps by ProMeTra-aeration-dependent gene expression and metabolism of Corynebacterium glutamicum as an example. BMC Syst Biol 3: 82.