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DksA DNA-binding transcriptional dual regulator

Summary:
The DksA protein binds directly to RNA polymerase, affecting transcript elongation and potentiating allosterically the effect of the alarmone ppGpp on transcription initiation 15294156. 29478808. DksA binding to the RNA polymerase (RNAP) secondary channel interferes with the proper ribonucleotide positioning in the RNAP active site, decreasing open complex stability but only at promoters with intrinsically unstable open complexes, such as the ribosomal promoters 25916853 DksA together with ppGpp is required for regulation of transcription of ribosomal RNA promoters Paul BJ,2004. DksA and ppGpp independently reduce transcription of the rrsBp1 promoter. The additions of both ppGpp and DksA have independent cumulative effects on transcription inhibition of the rrsBp1 promoter 25916853
DksA is involved in translational regulation of RpoS Brown L,2002.
dksA mutants have pleiotropic phenotypes. A null mutant is viable Kang PJ,1990. A dksA mutant exhibited a defect in induction of RpoS production upon entry into stationary phase 12193624 or in the presence of ppGpp Brown L,2002. A dksA mutant exhibited a complex phenotype with respect to ppGpp regulation Brown L,2002.
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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, argX, dksA, fimB, flu, gltT, gltU, gltV, gltW, gluQ, hisR, idlP, ileT, ileU, ileV, iraD, isrC, leuT, proM, rpoE, rrfA, rrfB, rrfC, rrfD, rrfE, rrfF, rrfG, rrfH, rrlA, rrlB, rrlC, rrlD, rrlE, rrlG, rrlH, rrsA, rrsB, rrsC, rrsD, rrsE, rrsG, rrsH, rseA, rseB, rseC, rybB, setA, sgrR, sgrS, sgrT, sroA, thiB, thiP, thiQ, thrV, ytiC, ytiD
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
translation (23)
rRNA, stable RNA (22)
ribosomes (22)
tRNA (15)
other (mechanical, nutritional, oxidative stress) (6)
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Regulated operon(s) argX-hisR-leuT-proM, fimB, isrC-flu, 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, sgrR-sroA-thiBPQ, sgrST-setA, ytiCD-idlP-iraD
First gene in the operon(s) argX, dksA, fimB, ytiC, idlP, isrC, rpoE, rrsA, rrsB, rrsC, rrsD, rrsE, rrsG, rrsH, rseA, rybB, sgrR, sgrS
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 activation argXp Sigma70 nd nd argX, hisR, leuT, proM nd nd [IDA] [1]
  DksA inhibition dksAp2 Sigma70 nd nd dksA, gluQ nd nd [APPH], [GEA], [IMP] [2], [3]
  DksA activation fimBp2 nd nd nd fimB nd nd [APPH], [GEA] [4]
  DksA activation flup Sigma70 nd nd isrC, flu nd nd [GEA] [5]
  DksA inhibition idlPp Sigma38 nd nd idlP, iraD nd nd [GEA], [IMP] [6]
  DksA inhibition iraDp1 Sigma70 nd nd ytiC, ytiD, idlP, iraD nd nd [GEA], [IMP] [6]
  DksA activation rpoEp Sigma24 nd nd rpoE, rseA, rseB, rseC nd nd [GEA] [7]
  DksA activation rpoEp2a Sigma70 nd nd rpoE, rseA, rseB, rseC nd nd [GEA] [7]
  DksA inhibition rrsAp Sigma32 nd nd rrsA, ileT, alaT, rrlA, rrfA nd nd [APPH], [GEA] [8]
  DksA inhibition rrsAp1 Sigma70 nd nd rrsA, ileT, alaT, rrlA, rrfA nd nd [APPH], [GEA] [8]
  DksA inhibition rrsBp Sigma32 nd nd rrsB, gltT, rrlB, rrfB nd nd [APPH], [GEA] [8]
  DksA inhibition rrsBp1 Sigma70 nd nd rrsB, gltT, rrlB, rrfB nd nd [APPH], [GEA] [8]
  DksA inhibition rrsCp Sigma32 nd nd rrsC, gltU, rrlC, rrfC nd nd [APPH], [GEA] [8]
  DksA inhibition rrsCp1 Sigma70 nd nd rrsC, gltU, rrlC, rrfC nd nd [APPH], [GEA] [8]
  DksA inhibition rrsDp Sigma32 nd nd rrsD, ileU, alaU, rrlD, rrfD, thrV, rrfF nd nd [APPH], [GEA] [8]
  DksA inhibition rrsDp1 Sigma70 nd nd rrsD, ileU, alaU, rrlD, rrfD, thrV, rrfF nd nd [APPH], [GEA] [8]
  DksA inhibition rrsEp Sigma70 nd nd rrsE, gltV, rrlE, rrfE nd nd [APPH], [GEA] [8]
  DksA inhibition rrsEp3 Sigma32 nd nd rrsE, gltV, rrlE, rrfE nd nd [APPH], [GEA] [8]
  DksA inhibition rrsGp Sigma32 nd nd rrsG, gltW, rrlG, rrfG nd nd [APPH], [GEA] [8]
  DksA inhibition rrsGp1 Sigma70 nd nd rrsG, gltW, rrlG, rrfG nd nd [APPH], [GEA] [8]
  DksA inhibition rrsHp Sigma32 nd nd rrsH, ileV, alaV, rrlH, rrfH nd nd [APPH], [GEA] [8]
  DksA inhibition rrsHp1 Sigma70 nd nd rrsH, ileV, alaV, rrlH, rrfH nd nd [APPH], [GEA] [8]
  DksA activation rseAp3 Sigma24 nd nd rseA, rseB, rseC nd nd [BPP], [IEP] [9]
  DksA activation rybBp Sigma24 nd nd rybB nd nd [BPP], [IEP] [9]
  DksA activation sgrRp Sigma70 nd nd sgrR, sroA, thiB, thiP, thiQ nd nd [GEA] [10]
  DksA activation sgrSp2 Sigma38 nd nd sgrS, sgrT, setA nd nd [GEA] [10]


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] 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

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

 [3] Edwards AN., Patterson-Fortin LM., Vakulskas CA., Mercante JW., Potrykus K., Vinella D., Camacho MI., Fields JA., Thompson SA., Georgellis D., Cashel M., Babitzke P., Romeo T., 2011, Circuitry linking the Csr and stringent response global regulatory systems., Mol Microbiol 80(6):1561-80

 [4] 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

 [5] Cabrer-Panes JD., Fernandez-Coll L., Fernandez-Vazquez J., Gaviria-Cantin TC., El Mouali Y., Åberg A., Balsalobre C., 2020, ppGpp mediates the growth phase-dependent regulation of agn43, a phase variable gene, by stimulating its promoter activity., Environ Microbiol Rep 12(4):444-453

 [6] Merrikh H., Ferrazzoli AE., Lovett ST., 2009, Growth phase and (p)ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli., J Bacteriol 191(24):7436-46

 [7] 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

 [8] 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

 [9] 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

 [10] Kessler JR., Cobe BL., Richards GR., 2017, Stringent Response Regulators Contribute to Recovery from Glucose Phosphate Stress in Escherichia coli., Appl Environ Microbiol 83(24)



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