RegulonDB RegulonDB 11.2: Operon Form
   

nrfABCDEFG operon and associated TUs in Escherichia coli K-12 genome




Operon      
Name: nrfABCDEFG
This page displays every known transcription unit of this operon and their known regulation.


Transcription unit          
Name: nrfABCDEFG
Synonym(s): OP00279, nrf
Gene(s): nrfA, nrfB, nrfC, nrfD, nrfE, nrfF, nrfG   Genome Browser M3D Gene expression COLOMBOS
Note(s): nrfA operon regulation is complex and is affected by different protein factors. Under anaerobic conditions, FNR activates binding at the -41.5 site, but its activation is repressed by IHF at the -55 site. When nitrate or nitrite is present, NarL is activated (via NarX or NarQ) and, upon binding to its target site, IHF is displaced and derepresses the FNR site to allow its dependent activation. Fis binding plays a central role in the catabolite repression of the nrf operon. Therefore, activation involving FNR, NarL, and IHF is thwarted by Fis when it binds to its target at position -15 and blocks access to the nrf promoter -10 element Browning DF,2005.
IHF can also activate the transcription of the nrf operon in an FNR-dependent way when it is bound to the site located at bp -179 from the promoter, but only when NarL and NarP are absent Browning DF,2006
nrfA expression is downregulated by NsrR, which is independent of IHF-dependent regulation Browning DF,2010. NsrR acts as a fine-tuner because it modulates nrfA activity rather than switching it off completely Browning DF,2010.
Based on a DNA sampling method, HU and YfhH were determined to be regulating the nrfA gene in vivo Browning DF,2010. HU activates nrfABCDEFG operon expression during exponential growth Oberto J, Nabti S, Jooste V, Mignot H, Rouviere-Yaniv J,2009.
nrfABCDEFG was significantly upregulated in response to quinonas anthraquinone-2-sulfonate (AQSim) reduction and azo dye acid red 18 (AR 18) decolorization under anaerobic conditions Zhang HK, Lu H, Wang J, Liu GF, Zhou JT, Xu MY,2013.
Reference(s): [1] Hussain H., et al., 1994
Promoter
Name: nrfAp
+1: 4287671
Sigma Factor: Sigma70 Sigmulon
Distance from start of the gene: 93
Sequence: atgcacttacaattgattaaagacaacattcacagtgtggttatttgttacacataggggCgagcaatgtcatgacagtgt
                            -35                  -10        +1                   
Note(s): Nitrate causes repression of the nrfAp promoter in a NarL- or a NarP-protein-dependent way, while repression of the same promoter by nitrite is mainly dependent on the NarP protein Stewart V,2003
Evidence: [COMP-AINF]
[EXP-IDA-TRANSCRIPTION-INIT-MAPPING]
[EXP-IMP]
Reference(s): [2] Darwin A., et al., 1993
[3] Huerta AM., et al., 2003
[4] Tyson KL., et al., 1994
TF binding sites (TFBSs)
[FNR,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal FNR activator nrfAp 4287623 4287636 -41.5 gcacttacaaTTGATTAAAGACAAcattcacagt nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-SEQ], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [11], [12]
[Fis,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal Fis repressor nrfAp 4287649 4287663 -15.0 ttcacagtgtGGTTATTTGTTACACataggggcga nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-CHIP-EXO], [EXP-CHIP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] W [5], [10], [11]
[FlhDC,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd FlhDC activator nrfAp nd nd nd nd nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS] W [16]
[IHF,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote IHF activator nrfAp 4287538 4287550 -127.0 tgattaattcTTTGAGGAACATGcagttatgca nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [5], [6], [7]
[IHF,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal IHF repressor nrfAp 4287610 4287622 -55.0 tggtattttaCATGCACTTACAAttgattaaag nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] W [5], [10], [11]
[NarL,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal NarL-phosphorylated activator nrfAp 4287589 4287595 -79.0 agatactgacTAACTCTaaagtggtat nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [11], [12], [13], [14]
proximal NarL-phosphorylated activator nrfAp 4287598 4287604 -70.0 ctaactctaaAGTGGTAttttacatgc nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-CHIP-EXO], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [11], [12], [13], [14]
proximal NarL-phosphorylated activator nrfAp 4287618 4287624 -50.0 tacatgcactTACAATTgattaaagac nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [12], [13], [14]
[NarL,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal NarL-phosphorylated repressor nrfAp 4287618 4287624 -50.0 tacatgcactTACAATTgattaaagac nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [12], [13], [14]
proximal NarL-phosphorylated repressor nrfAp 4287646 4287652 -22.0 acattcacagTGTGGTTatttgttaca nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [12], [13], [14]
[NarP,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal NarP-phosphorylated activator nrfAp 4287584 4287599 -79.0 gaggaagataCTGACTAACTCTAAAGtggtatttta nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [11], [12], [13], [14]
proximal NarP-phosphorylated activator nrfAp 4287593 4287608 -70.0 actgactaacTCTAAAGTGGTATTTTacatgcactt nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [4], [10], [11], [12], [13], [14]
[NsrR,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote NsrR repressor nrfAp 4287545 4287556 -121.0 ttctttgaggAACATGCAGTTAtgcatgctgt nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [8], [9]
proximal NsrR repressor nrfAp 4287599 4287617 -63.0 taactctaaaGTGGTATTTTACATGCACTtacaattgat nd [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IMP-SITE-MUTATION] C [9], [15]


RNA cis-regulatory element    
Regulation, transcriptional elongation  
Attenuator type: Translational
Strand: forward
  Structure type Energy LeftPos RightPos Sequence (RNA-strand)
  terminator -9.6 4287726 4287744 aataaaaaccGCCATTGCAACAATGGCGcaattcggat
Notes: "The provided "Sequence" is that of the RNA strand, i.e. U's are shown instead of T's and regulators on the reverse strand will appear as the reverse complement of the sequence delimited by LeftPos-RigtPos"


Evidence    

 [COMP-AINF] Inferred computationally without human oversight

 [EXP-IDA-TRANSCRIPTION-INIT-MAPPING] Transcription initiation mapping

 [EXP-IMP] Inferred from mutant phenotype

 [EXP-IEP-GENE-EXPRESSION-ANALYSIS] Gene expression analysis

 [EXP-CHIP-SEQ] high throughput ChIP-seq evidence

 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] Binding of cellular extracts

 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] Binding of purified proteins

 [EXP-CHIP-EXO] high throughput ChIP-exo evidence

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences

 [EXP-IMP-SITE-MUTATION] Site mutation

 [EXP-DAP-SEQ] high throughput DNA Affinity Purification (DAP) Sequencing

 [COMP-HINF-SIMILAR-TO-CONSENSUS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.


Reference(s)    

 [1] Hussain H., Grove J., Griffiths L., Busby S., Cole J., 1994, A seven-gene operon essential for formate-dependent nitrite reduction to ammonia by enteric bacteria., Mol Microbiol 12(1):153-63

 [2] Darwin A., Hussain H., Griffiths L., Grove J., Sambongi Y., Busby S., Cole J., 1993, Regulation and sequence of the structural gene for cytochrome c552 from Escherichia coli: not a hexahaem but a 50 kDa tetrahaem nitrite reductase., Mol Microbiol 9(6):1255-65

 [3] Huerta AM., Collado-Vides J., 2003, Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals., J Mol Biol 333(2):261-78

 [4] Tyson KL., Cole JA., Busby SJ., 1994, Nitrite and nitrate regulation at the promoters of two Escherichia coli operons encoding nitrite reductase: identification of common target heptamers for both NarP- and NarL-dependent regulation., Mol Microbiol 13(6):1045-55

 [5] Browning DF., Beatty CM., Sanstad EA., Gunn KE., Busby SJ., Wolfe AJ., 2004, Modulation of CRP-dependent transcription at the Escherichia coli acsP2 promoter by nucleoprotein complexes: anti-activation by the nucleoid proteins FIS and IHF., Mol Microbiol 51(1):241-54

 [6] Browning DF., Lee DJ., Wolfe AJ., Cole JA., Busby SJ., 2006, The Escherichia coli K-12 NarL and NarP proteins insulate the nrf promoter from the effects of integration host factor., J Bacteriol 188(21):7449-56

 [7] Sclavi B., Beatty CM., Thach DS., Fredericks CE., Buckle M., Wolfe AJ., 2007, The multiple roles of CRP at the complex acs promoter depend on activation region 2 and IHF., Mol Microbiol 65(2):425-40

 [8] Filenko N., Spiro S., Browning DF., Squire D., Overton TW., Cole J., Constantinidou C., 2007, The NsrR regulon of Escherichia coli K-12 includes genes encoding the hybrid cluster protein and the periplasmic, respiratory nitrite reductase., J Bacteriol 189(12):4410-7

 [9] Partridge JD., Bodenmiller DM., Humphrys MS., Spiro S., 2009, NsrR targets in the Escherichia coli genome: new insights into DNA sequence requirements for binding and a role for NsrR in the regulation of motility., Mol Microbiol 73(4):680-94

 [10] Browning DF., Beatty CM., Wolfe AJ., Cole JA., Busby SJ., 2002, Independent regulation of the divergent Escherichia coli nrfA and acsP1 promoters by a nucleoprotein assembly at a shared regulatory region., Mol Microbiol 43(3):687-701

 [11] Browning DF., Grainger DC., Beatty CM., Wolfe AJ., Cole JA., Busby SJ., 2005, Integration of three signals at the Escherichia coli nrf promoter: a role for Fis protein in catabolite repression., Mol Microbiol 57(2):496-510

 [12] Darwin AJ., Tyson KL., Busby SJ., Stewart V., 1997, Differential regulation by the homologous response regulators NarL and NarP of Escherichia coli K-12 depends on DNA binding site arrangement., Mol Microbiol 25(3):583-95

 [13] Rabin RS., Stewart V., 1993, Dual response regulators (NarL and NarP) interact with dual sensors (NarX and NarQ) to control nitrate- and nitrite-regulated gene expression in Escherichia coli K-12., J Bacteriol 175(11):3259-68

 [14] Wang H., Gunsalus RP., 2000, The nrfA and nirB nitrite reductase operons in Escherichia coli are expressed differently in response to nitrate than to nitrite., J Bacteriol 182(20):5813-22

 [15] Browning DF., Lee DJ., Spiro S., Busby SJ., 2010, Down-regulation of the Escherichia coli K-12 nrf promoter by binding of the NsrR nitric oxide-sensing transcription repressor to an upstream site., J Bacteriol 192(14):3824-8

 [16] Pruss BM., Liu X., Hendrickson W., Matsumura P., 2001, FlhD/FlhC-regulated promoters analyzed by gene array and lacZ gene fusions., FEMS Microbiol Lett 197(1):91-7

RegulonDB