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DksA-ppGpp DNA-binding transcriptional dual regulator

Summary:
DksA and ppGpp increase σS holoenzyme activity Brown L,2002
Effects on unknown factors or solution conditions such as pH, salt, and template conformation can allow DksA to activate specific promoters in the absence of ppGpp Girard ME,2018
A novel role for DksA and ppGpp in contributing to the recovery from glucose phosphate stress was determined Kessler JR,2017


Transcription factor      
Gene name: dksA
  Genome position: 160149-160604
  Length: 456 bp / 151 aa
Operon name: sfsA-dksA-gluQ
TU(s) encoding the TF:
Transcription unit        Promoter
dksA-gluQ
dksAp3
dksA-yadB
dksAp1
dksA-yadB
dksAp2
sfsA-dksA
sfsAp


Regulon       
Regulated gene(s) alaT, alaU, alaV, argI, argX, dksA, dnaG, dsrA, dusB, fabD, fabG, fabH, fadR, fimB, fis, folK, fusA, gltT, gltU, gltV, gltW, gluQ, hisA, hisB, hisC, hisD, hisF, hisG, hisH, hisI, hisL, hisR, hlyE, ihfA, ihfB, ileT, ileU, ileV, infC, iraP, leuT, livJ, mutM, obgE, pcnB, pheM, pheS, pheT, proM, recG, rimM, rplA, rplB, rplC, rplD, rplE, rplF, rplJ, rplK, rplL, rplM, rplN, rplO, rplP, rplQ,
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Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
translation (73)
ribosomes (69)
ribosomal proteins (47)
rRNA, stable RNA (22)
tRNA (15)
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Regulated operon(s) argI, argX-hisR-leuT-proM, cmk-rpsA-ihfB, dsrA, dusB-fis, fadR, fimB, hisLGDCBHAFI, hlyE, iraP, livJ, nlpD-rpoS, pcnB-folK, rplKAJL-rpoBC, rplM-rpsI, rplNXE-rpsNH-rplFR-rpsE-rpmD-rplO-secY-rpmJ, rplU-rpmA-yhbE-obgE, rplY, rpoZ-spoT-trmH-recG, rpsJ-rplCDWB-rpsS-rplV-rpsC-rplP-rpmC-rpsQ, rpsLG-fusA-tufA, rpsMKD-rpoA-rplQ, rpsP-rimM-trmD-rplS, rpsT, rpsU-dnaG-rpoD, rrsA-ileT-alaT-rrlA-rrfA, rrsB-gltT-rrlB-rrfB, rrsC-gltU-rrlC-rrfC, rrsD-ileU-alaU-rrlD-rrfD-thrV-rrfF, rrsE-gltV-rrlE-rrfE, rrsG-gltW-rrlG-rrfG, rrsH-ileV-alaV-rrlH-rrfH, rseD-rpoE-rseABC, rybB, sfsA-dksA-gluQ, thrLABC, thrS-infC-rpmI-rplT-pheMST-ihfA, yceD-rpmF-plsX-fabHDG-acpP-fabF, yicR-rpmBG-mutM
First gene in the operon(s) argI, argX, dksA, dsrA, dusB, fabH, fadR, fimB, hisL, hlyE, infC, iraP, livJ, pcnB, rplJ, rplK, rplM, rplN, rplU, rpmB, rpmI, rpoE, rpoS, rpoZ, rpsA, rpsJ, rpsL, rpsM, rpsP, rpsT, rpsU, rrsA, rrsB, rrsC, rrsD, rrsE, rrsG, rrsH, rseA, rybB, thrL, thrS, rplY
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  DksA-ppGpp activation argIp Sigma70 nd nd argI nd nd [APPH], [IMP] [1]
  DksA-ppGpp inhibition argXp Sigma70 nd nd argX, hisR, leuT, proM nd nd [IDA] [2]
  DksA-ppGpp inhibition dksAp2 Sigma70 nd nd dksA, gluQ nd nd [APPH], [GEA], [IMP] [3]
  DksA-ppGpp activation dsrAp Sigma70 nd nd dsrA nd nd [APPH], [GEA] [4]
  DksA-ppGpp inhibition dusBp Sigma70 nd nd dusB, fis nd nd [APPH], [GEA], [IMP] [5]
  DksA-ppGpp inhibition fabHp nd nd nd fabH, fabD, fabG nd nd [GEA] [6], [7]
  DksA-ppGpp inhibition fadRp Sigma70 nd nd fadR nd nd [GEA] [6]
  DksA-ppGpp activation fimBp2 nd nd nd fimB nd nd [BPP], [GEA] [8]
  DksA-ppGpp activation hisLp nd nd nd hisL, hisG, hisD, hisC, hisB, hisH, hisA, hisF, hisI nd nd [IDA] [9]
  DksA-ppGpp activation hlyEp nd nd nd hlyE nd nd [GEA] [10]
  DksA-ppGpp inhibition infCp nd nd nd infC nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition infCp2 Sigma70 nd nd infC, rpmI, rplT nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp activation iraPp1 Sigma70 nd nd iraP nd nd [APPH], [GEA] [4], [12], [13]
  DksA-ppGpp activation livJp Sigma70 nd nd livJ nd nd [APPH], [IMP] [1], [9]
  DksA-ppGpp inhibition pcnBp Sigma38 nd nd pcnB, folK nd nd [APPH], [GEA] [14]
  DksA-ppGpp inhibition pcnBp4 Sigma38 nd nd pcnB, folK nd nd [GEA] [14]
  DksA-ppGpp inhibition rplJp nd nd nd rplJ, rplL, rpoB, rpoC nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rplKp nd nd nd rplK, rplA, rplJ, rplL, rpoB, rpoC nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rplMp nd nd nd rplM, rpsI nd nd [GEA] [15]
  DksA-ppGpp inhibition rplNp nd nd nd rplN, rplX, rplE, rpsN, rpsH, rplF, rplR, rpsE, rpmD, rplO, secY, rpmJ nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rplUp Sigma70 nd nd rplU, rpmA, yhbE, obgE nd nd [GEA] [15]
  DksA-ppGpp inhibition rplVp Sigma70 nd nd rplY nd nd [GEA] [16]
  DksA-ppGpp inhibition rpmBp nd nd nd rpmB, rpmG, mutM nd nd [GEA] [15]
  DksA-ppGpp inhibition rpmIp Sigma70 nd nd rpmI, rplT nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp activation rpoEp Sigma24 nd nd rpoE, rseA, rseB, rseC nd nd [GEA] [17]
  DksA-ppGpp activation rpoEp2a Sigma70 nd nd rpoE, rseA, rseB, rseC nd nd [GEA] [17]
  DksA-ppGpp activation rpoSp1 nd nd nd rpoS nd nd [GEA] [17]
  DksA-ppGpp inhibition rpoZp Sigma70 nd nd rpoZ, spoT, trmH, recG nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsAp1 Sigma70 nd nd rpsA, ihfB nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsAp3 Sigma70 nd nd rpsA, ihfB nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsJp Sigma70 nd nd rpsJ, rplC, rplD, rplW, rplB, rpsS, rplV, rpsC, rplP, rpmC, rpsQ nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsLp nd nd nd rpsL, rpsG, fusA, tufA nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsMp2 Sigma70 nd nd rpsM, rpsK, rpsD, rpoA, rplQ nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsPp Sigma70 nd nd rpsP, rimM, trmD, rplS nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsTp1 nd nd nd rpsT nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsTp2 nd nd nd rpsT nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rpsUp2 Sigma70 nd nd rpsU, dnaG, rpoD nd nd [APPH], [GEA], [IMP] [11]
  DksA-ppGpp inhibition rrsAp Sigma32 nd nd rrsA, ileT, alaT, rrlA, rrfA nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsAp1 Sigma70 nd nd rrsA, ileT, alaT, rrlA, rrfA nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsBp Sigma32 nd nd rrsB, gltT, rrlB, rrfB nd nd [APPH], [GEA], [IEP], [IMP], [IPI] [18], [19], [20]
  DksA-ppGpp inhibition rrsBp1 Sigma70 nd nd rrsB, gltT, rrlB, rrfB nd nd [APPH], [GEA], [IEP], [IMP], [IPI] [18], [19], [20]
  DksA-ppGpp inhibition rrsCp Sigma32 nd nd rrsC, gltU, rrlC, rrfC nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsCp1 Sigma70 nd nd rrsC, gltU, rrlC, rrfC nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsDp Sigma32 nd nd rrsD, ileU, alaU, rrlD, rrfD, thrV, rrfF nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsDp1 Sigma70 nd nd rrsD, ileU, alaU, rrlD, rrfD, thrV, rrfF nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsEp Sigma70 nd nd rrsE, gltV, rrlE, rrfE nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsEp3 Sigma32 nd nd rrsE, gltV, rrlE, rrfE nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsGp Sigma32 nd nd rrsG, gltW, rrlG, rrfG nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsGp1 Sigma70 nd nd rrsG, gltW, rrlG, rrfG nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsHp Sigma32 nd nd rrsH, ileV, alaV, rrlH, rrfH nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp inhibition rrsHp1 Sigma70 nd nd rrsH, ileV, alaV, rrlH, rrfH nd nd [APPH], [GEA], [IMP] [18]
  DksA-ppGpp activation rseAp3 Sigma24 nd nd rseA, rseB, rseC nd nd [BPP], [IEP] [21]
  DksA-ppGpp activation rybBp Sigma24 nd nd rybB nd nd [BPP], [IEP] [21]
  DksA-ppGpp activation thrLp Sigma70 nd nd thrL, thrA, thrB, thrC nd nd [APPH], [IEP] [9], [19]
  DksA-ppGpp inhibition thrSp nd nd nd thrS, infC, rpmI, rplT, pheM, pheS, pheT, ihfA nd nd [APPH], [GEA], [IMP] [11]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation




Reference(s)    

 [1] Paul BJ., Berkmen MB., Gourse RL., 2005, DksA potentiates direct activation of amino acid promoters by ppGpp., Proc Natl Acad Sci U S A 102(22):7823-8

 [2] Lyzen R., Maitra A., Milewska K., Kochanowska-Lyzen M., Hernandez VJ., Szalewska-Palasz A., 2016, The dual role of DksA protein in the regulation of Escherichia coli pArgX promoter., Nucleic Acids Res 44(21):10316-10325

 [3] Chandrangsu P., Lemke JJ., Gourse RL., 2011, The dksA promoter is negatively feedback regulated by DksA and ppGpp., Mol Microbiol 80(5):1337-48

 [4] Girard ME., Gopalkrishnan S., Grace ED., Halliday JA., Gourse RL., Herman C., 2018, DksA and ppGpp Regulate the σS Stress Response by Activating Promoters for the Small RNA DsrA and the Anti-Adapter Protein IraP., J Bacteriol 200(2)

 [5] Mallik P., Paul BJ., Rutherford ST., Gourse RL., Osuna R., 2006, DksA is required for growth phase-dependent regulation, growth rate-dependent control, and stringent control of fis expression in Escherichia coli., J Bacteriol 188(16):5775-82

 [6] My L., Rekoske B., Lemke JJ., Viala JP., Gourse RL., Bouveret E., 2013, Transcription of the Escherichia coli Fatty Acid Synthesis Operon fabHDG Is Directly Activated by FadR and Inhibited by ppGpp., J Bacteriol 195(16):3784-95

 [7] Podkovyrov SM., Larson TJ., 1996, Identification of promoter and stringent regulation of transcription of the fabH, fabD and fabG genes encoding fatty acid biosynthetic enzymes of Escherichia coli., Nucleic Acids Res 24(9):1747-52

 [8] Aberg A., Shingler V., Balsalobre C., 2008, Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo., Mol Microbiol 67(6):1223-41

 [9] Lee JH., Lennon CW., Ross W., Gourse RL., 2012, Role of the coiled-coil tip of Escherichia coli DksA in promoter control., J Mol Biol 416(4):503-17

 [10] Bartoli J., Viala JP., Bouveret E., 2020, SlyA Transcriptional Regulator Is Not Directly Affected by ppGpp Levels., Front Microbiol 11:1856

 [11] Lemke JJ., Sanchez-Vazquez P., Burgos HL., Hedberg G., Ross W., Gourse RL., 2011, Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA., Proc Natl Acad Sci U S A 108(14):5712-7

 [12] Bougdour A., Gottesman S., 2007, ppGpp regulation of RpoS degradation via anti-adaptor protein IraP., Proc Natl Acad Sci U S A 104(31):12896-901

 [13] Ross W., Sanchez-Vazquez P., Chen AY., Lee JH., Burgos HL., Gourse RL., 2016, ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response., Mol Cell 62(6):811-823

 [14] Nadratowska-Wesolowska B., Slominska-Wojewodzka M., Lyzen R., Wegrzyn A., Szalewska-Palasz A., Wegrzyn G., 2010, Transcription regulation of the Escherichia coli pcnB gene coding for poly(A) polymerase I: roles of ppGpp, DksA and sigma factors., Mol Genet Genomics 284(4):289-305

 [15] Aseev LV., Koledinskaya LS., Boni IV., 2016, Regulation of Ribosomal Protein Operons rplM-rpsI, rpmB-rpmG, and rplU-rpmA at the Transcriptional and Translational Levels., J Bacteriol 198(18):2494-502

 [16] Aseev LV., Bylinkina NS., Boni IV., 2015, Regulation of the rplY gene encoding 5S rRNA binding protein L25 in Escherichia coli and related bacteria., RNA 21(5):851-61

 [17] Gopalkrishnan S., Nicoloff H., Ades SE., 2014, Co-ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes., Mol Microbiol 93(3):479-93

 [18] Paul BJ., Barker MM., Ross W., Schneider DA., Webb C., Foster JW., Gourse RL., 2004, DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP., Cell 118(3):311-22

 [19] Mechold U., Potrykus K., Murphy H., Murakami KS., Cashel M., 2013, Differential regulation by ppGpp versus pppGpp in Escherichia coli., Nucleic Acids Res 41(12):6175-89

 [20] Pupov D., Petushkov I., Esyunina D., Murakami KS., Kulbachinskiy A., 2018, Region 3.2 of the σ factor controls the stability of rRNA promoter complexes and potentiates their repression by DksA., Nucleic Acids Res 46(21):11477-11487

 [21] Costanzo A., Nicoloff H., Barchinger SE., Banta AB., Gourse RL., Ades SE., 2008, ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor sigmaE in Escherichia coli by both direct and indirect mechanisms., Mol Microbiol 67(3):619-32



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