RegulonDB RegulonDB 11.0: Operon Form

isrC-flu operon and associated TUs in Escherichia coli K-12 genome

Name: isrC-flu
This page displays every known transcription unit of this operon and their known regulation.

Transcription unit          
Name: isrC-flu
Synonym(s): agn43
Gene(s): isrC, flu   Genome Browser M3D Gene expression COLOMBOS
Note(s): The OxyR-binding site in the regulatory region of the flu gene contains three GATC sequences that are recognized by the protein Dam for methylation. When this DNA region is methylated, OxyR cannot bind it to repress the expression of the flu gene. Conversely, when OxyR is bound to this region, the Dam protein cannot methylate the DNA in this region Correnti J,2002.
Both oxidized and reduced forms of OxyR bind to hemimethylated DNA with lower affinity than the unmethylated DNA Correnti J,2002.
Expression of flu is phase variable and is characterized by its ON phase (OxyR impedes flu transcription) and OFF phase (Dam methylates GATC sites at the OxyR-binding site, and flu can be expressed) Chauhan A,2013. flu ON/OFF phases strongly induce autoagregation and biofilm formation Chauhan A,2013. Based on transcriptomic analysis, it has been shown that flu is regulated by both MqsR Gonzalez Barrios AF,2006 and Lrp Tani TH, Khodursky A, Blumenthal RM, Brown PO, Matthews RG,2002. However, it was shown that these regulators do not control flu expression or the ON/OFF switch frequency Chauhan A,2013.
Evidence: [BTEI] Boundaries of transcription experimentally identified
Reference(s): [1] Henderson IR., et al., 1999
[2] Waldron DE., et al., 2002
Name: flup
+1: 2071317
Sigma Factor: Sigma70 Sigmulon
Distance from start of the gene: 0
Sequence: aagcactgttttcgttactgtctctcttgtccgtgcaatagctcaataatagaataaaacGatcaatatctattttatcga
                           -35                    -10       +1                   
Note(s): The activity of the flup promoter is increased by a mutation in the rpoA gene, which codes for a subunit of the RNA polymerase. On the other hand, the activity of the promoter is depressed in the presence of deoxycholate and lactose Gabig M, Herman-Antosiewicz A, Kwiatkowska M, Los M, Thomas MS, Wegrzyn G,2002.
RpoS does not regulate the flup promoter Cabrer-Panes JD,2020.
Evidence: [HIPP]
Reference(s): [3] Huerta AM., et al., 2003
[2] Waldron DE., et al., 2002
Type: rho-independent
Reference(s): [4] Wallecha A., et al., 2014
TF binding sites (TFBSs)
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal OxyR repressor flup 2071283 2071299 -26.0 actgtctctcTTGTCCGTGCAATAGCTcaataataga nd [RSE], [CEEUMA], [IHBCE] [5]
proximal OxyR repressor flup 2071310 2071326 2.0 caataatagaATAAAACGATCAATATCtattttatcg nd [GEA], [APIORCISFBSCS], [BPP], [SM] [1], [2], [6], [7], [8]
proximal OxyR repressor flup 2071332 2071348 24.0 atatctatttTATCGATCGTTTATATCgatcgataag nd [GEA], [RSE], [APIORCISFBSCS], [BPP], [CEEUMA], [IHBCE], [SM] [1], [2], [5], [6], [7], [8]
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd YdcI activator flup nd nd nd nd nd [GEA], [RSE], [BPP] [9]
Allosteric regulation of RNA-polymerase
  Regulator Function Promoter target of RNApol Growth Conditions Note Evidence Reference
  DksA activation flup nd   [GEA] [10]
  ppGpp activation flup nd   [GEA] [10]
Evidence: [GEA] Gene expression analysis
Reference(s): [10] Cabrer-Panes JD., et al., 2020

Transcription unit       
Name: flu
Gene(s): flu   Genome Browser M3D Gene expression COLOMBOS
Evidence: [IC] Inferred by curator
Name: flup1
+1: 2071474
Distance from start of the gene: 65
Sequence: gaacaacagaaccacaattcagaaactcccacagccggacctccggcactgtaaccctttAcctgccggtatccacgtttg
Evidence: [HTTIM]
Reference(s): [11] Mendoza-Vargas A., et al., 2009

Transcription unit       
Name: flu
Gene(s): flu   Genome Browser M3D Gene expression COLOMBOS
Evidence: [IC] Inferred by curator
Name: flup2
+1: 2071503
Distance from start of the gene: 36
Sequence: cacagccggacctccggcactgtaaccctttacctgccggtatccacgtttgtgggtaccGgcttttttattcaccctcaa
Evidence: [HTTIM]
Reference(s): [11] Mendoza-Vargas A., et al., 2009

Transcription unit       
Name: isrC
Gene(s): isrC   Genome Browser M3D Gene expression COLOMBOS
Evidence: [IHBCE] Inferred by a human based on computational evidence

RNA cis-regulatory element    
Regulation, transcriptional elongation  
Attenuator type: Transcriptional
Strand: forward
  Structure type Energy LeftPos RightPos Sequence (RNA-strand)
  terminator -21.9 2071478 2071514 cctttacctgCCGGTATCCACGTTTGTGGGTACCGGCTTTTTTATTcaccctcaat
  anti-terminator -14.3 2071446 2071492 aactcccacaGCCGGACCTCCGGCACTGTAACCCTTTACCTGCCGGTATCCACGTTtgtgggtacc
  anti-anti-terminator -9.4 2071444 2071465 gaaactcccaCAGCCGGACCTCCGGCACTGTaaccctttac
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"


 [1] Henderson IR., Owen P., 1999, The major phase-variable outer membrane protein of Escherichia coli structurally resembles the immunoglobulin A1 protease class of exported protein and is regulated by a novel mechanism involving Dam and oxyR., J Bacteriol 181(7):2132-41

 [2] Waldron DE., Owen P., Dorman CJ., 2002, Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli., Mol Microbiol 44(2):509-20

 [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] Wallecha A., Oreh H., van der Woude MW., deHaseth PL., 2014, Control of Gene Expression at a Bacterial Leader RNA, the agn43 Gene Encoding Outer Membrane Protein Ag43 of Escherichia coli., J Bacteriol 196(15):2728-35

 [5] Seo SW., Kim D., Szubin R., Palsson BO., 2015, Genome-wide Reconstruction of OxyR and SoxRS Transcriptional Regulatory Networks under Oxidative Stress in Escherichia coli K-12 MG1655., Cell Rep 12(8):1289-99

 [6] Haagmans W., van der Woude M., 2000, Phase variation of Ag43 in Escherichia coli: Dam-dependent methylation abrogates OxyR binding and OxyR-mediated repression of transcription., Mol Microbiol 35(4):877-87

 [7] Wallecha A., Correnti J., Munster V., van der Woude M., 2003, Phase variation of Ag43 is independent of the oxidation state of OxyR., J Bacteriol 185(7):2203-9

 [8] Wallecha A., Munster V., Correnti J., Chan T., van der Woude M., 2002, Dam- and OxyR-dependent phase variation of agn43: essential elements and evidence for a new role of DNA methylation., J Bacteriol 184(12):3338-47

 [9] Romiyo V., Wilson JW., 2020, Phenotypes, transcriptome, and novel biofilm formation associated with the ydcI gene., Antonie Van Leeuwenhoek 113(8):1109-1122

 [10] 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

 [11] Mendoza-Vargas A., Olvera L., Olvera M., Grande R., Vega-Alvarado L., Taboada B., Jimenez-Jacinto V., Salgado H., Juarez K., Contreras-Moreira B., Huerta AM., Collado-Vides J., Morett E., 2009, Genome-wide identification of transcription start sites, promoters and transcription factor binding sites in E. coli., PLoS One 4(10):e7526