RegulonDB RegulonDB 10.8: Operon Form
   

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




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


Transcription unit          
Name: flhDC
Synonym(s): OP00183
Gene(s): flhC, flhD   Genome Browser M3D Gene expression COLOMBOS
Note(s): The transcription of the flhDC operon is repressed in acidic phospholipid-deficient cells, but the gadW, metE, and yeaB genes in multicopy suppress this repression through the reduction of overexpression of RpoS caused by the same mutation in the gene producing acidic phospholipid 20185506 The mechanism for this is not known.
Under motility-inducing environmental growth conditions, a motile element (IS5) is inserted into the upstream region of the flhDC operon. This event appears to enhance the expression of the operon, because motility and biofilm formation are increased 21390082CITS: [28100305]|. IS5 insertion disrupts the H-NS binding site, thus preventing transcriptional repression of the operon 21390082 Three novel cis-acting IS elements upstream of flhDC (IS5, located at -166 and -315, IS1, inserted at -303, and a trans-acting missense mutation in lrhA) were found that enhanced motility by relieving transcriptional repression of flhDC 23456724 Both effects act in parallel, suggesting their apparently independent regulation of flagellar expression 23456724 Several insertion sequence (IS) elements upstream of the promoter for flhDC stimulate motility independently of orientation and have a long-range effect 26170415
fllhDC expression is enhanced by AtoSC in the presence of acetoacetate 22083893.
Under NlpE outer membrane lipoprotein overexpression, the transcription of the flhC gene is decreased Raivio TL,2013
In a study where it was shown that the L-tryptophan eradicated persister cells, it was observed that the exogenous amino acid downregulated the expression of flhDC as well as other flagellar genes 31271063.
Based on mutations analysis, it was shown that OmpR and RcsB abolish temporal and spatial changes in expression of flhDC 23914787
Single nucleotide changes in the -10 element and the spacer of the flhDC promoter, and also in the cAMP-CRP-binding region, increase motility 26170415
Several mutations in the flhDC promoter allow motility in H-NS mutant strains 26170415
YjjQ represses transcription of the flhDC operon independently from the previously characterized RcsA-RcsB repressor, even though the two DNA-binding motifs contain overlapping sequences Wiebe H,2015 flhDC requires a specific transcription rate to maintain optimal flagellum numbers 30420601
The impact of a two-component signal transduction system (2CSTS) was reviewed with regard to EnvZ/OmpT, RscCDB, CheAYB, and QueCB. Studies of the effects of changes in signaling on the expression of motility and biofilm genes revealed the involvement of the flhDC operon in the induction of changes in motility in the early phases of biofilm development and the swim-or-stick switch that allows bacteria to transit from reversible to irreversible attachment 28533218.
Orthologous flhDC from E. coli can functionally complement flhDC in S. Enterica, and flhCEC is not functionally identical to flhCST 30420601 The phenotypic differences between species arise from adaptations during evolution to expand or modify cellular function with respect to movement within specific environmental niches 30420601
The mRNA that contains the flhD gene has been observed mainly in the poles of the cell 31540875.
Evidence: [LTED] Length of transcript experimentally determined
Reference(s): [1] Bertin P., et al., 1994
[2] Lehti TA., et al., 2012
[3] Shin S., et al., 1995
Promoter
Name: flhDp
+1: 1978395
Sigma Factor: Sigma70 Sigmulon
Distance from start of the gene: 198
Sequence: tattgaaaatcgcagcccccctccgttgtatgtgcgtgtagtgacgagtacagttgcgtcGatttaggaaaaatcttagat
                          -35                    -10        +1                   
Evidence: [TIM]
Reference(s): [4] Barker CS., et al., 2004
[3] Shin S., et al., 1995
[5] Soutourina O., et al., 1999
[6] Wei BL., et al., 2001
Terminator(s)
Type: rho-independent
Sequence: ttaacgcgcgATTGGGGCAAAAAAAAGCAGCGGTACGTCGTTACCGCTGCTGGAATGTTGCGCCTcaccgtatca
Reference(s): [7] Feng CQ., et al., 2019
[8] Lesnik EA., et al., 2001
TF binding sites (TFBSs)
[AcrR,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal AcrR repressor flhDp 1978422 1978432 -31.5 agcccccctcCGTTGTATGTGcgtgtagtga nd [APIORCISFBSCS], [CV(GEA)], [GEA] [13]
[CRP,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal CRP-cAMP activator flhDp 1978456 1978477 -71.5 attgagtgttTTGTGTGATCTGCATCACGCATtattgaaaat nd [APIORCISFBSCS], [BPP], [CV(GEA)], [CV(GEA)], [GEA] [5], [10], [11], [12]
[FliZ,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal FliZ1 repressor flhDp 1978370 1978399 12.0 agtacagttgCGTCGATTTAGGAAAAATCTTAGATAAGTGtaaagaccca nd [BPP], [GEA] [17]
[Fur,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote Fur-Fe2+ repressor flhDp 1978272 1978290 115.0 caactattctAATGCTAATTATTTTTTACcggggcttcc nd [AIBSCS] [18]
[H-NS,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd H-NS activator flhDp nd nd nd nd nd [BPP], [GEA] [1], [5]
[HdfR,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd HdfR repressor flhDp nd nd nd nd nd [BPP], [GEA] [20]
[IHF,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal IHF repressor flhDp 1978481 1978493 -92.0 ccatttatgtTAAGTAATTGAGTgttttgtgtg nd [APIORCISFBSCS] [3]
[LrhA,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote LrhA repressor flhDp 1978500 1978514 -112.0 tcaataagttGGAGTCATTACCCATttatgttaag nd [BPP], [GEA] [9]
[MatA,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd MatA1 repressor flhDp nd nd nd nd nd [BPP], [GEA] [2]
[OmpR,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal OmpR-P repressor flhDp 1978368 1978387 18.5 tcgatttaggAAAAATCTTAGATAAGTGTAaagacccatt nd [APIORCISFBSCS] [3]
remote OmpR-P repressor flhDp 1978531 1978550 -145.5 caaagtcatcGGGCATTATCTGAACATAAAacactatcaa nd [APIORCISFBSCS] [3]
[QseB,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd QseB-Phosphorylated activator flhDp nd nd nd nd nd [GEA] [19]
[RcsAB,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal RcsAB1 repressor flhDp 1978378 1978392 11.0 ttgcgtcgatTTAGGAAAAATCTTAgataagtgta nd [BPP], [CV(SM)], [GEA], [SM] [15], [16]
[YjjQ,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal YjjQ repressor flhDp 1978378 1978392 11.0 ttgcgtcgatTTAGGAAAAATCTTAgataagtgta nd [AIBSCS], [CV(GEA)], [CV(GEA)], [CV(GEA/SM)], [CV(SM)], [GEA], [SM] [14]
Note(s): 1No DNA consensus sequence that is recognized by FliZ has been established. Therefore, for this DNA-binding site we added the complete region, determined by footprinting analysis Pesavento C,2012 to which FliZ binds.1MatA-flhDp regulatory interaction was identified in Escherichia coli strain IHE 3034 Lehti TA,2012
MatA binds with higher affinity to flhDp than flhDp2 Lehti TA,2012
1The binding of the RcsAB heterodimer might sterically prevent the accessibility of the flhDC promoter to the RNA polymerase, or alternatively it might lead to premature transcription termination.7The binding of the RcsAB heterodimer might sterically prevent the accessibility of the flhDC promoter to the RNA polymerase, or alternatively it might lead to premature transcription termination.
8No DNA consensus sequence that is recognized by FliZ has been established. Therefore, for this DNA-binding site we added the complete region, determined by footprinting analysis Pesavento C,2012 to which FliZ binds.
13MatA-flhDp regulatory interaction was identified in Escherichia coli strain IHE 3034 Lehti TA,2012
MatA binds with higher affinity to flhDp than flhDp2 Lehti TA,2012


Transcription unit          
Name: flhDC
Gene(s): flhC, flhD   Genome Browser M3D Gene expression COLOMBOS
Note(s): The transcription of the flhDC operon is repressed in acidic phospholipid-deficient cells, but the gadW, metE, and yeaB genes in multicopy suppress this repression through the reduction of overexpression of RpoS caused by the same mutation in the gene producing acidic phospholipid 20185506 The mechanism for this is not known.
Under motility-inducing environmental growth conditions, a motile element (IS5) is inserted into the upstream region of the flhDC operon. This event appears to enhance the expression of the operon, because motility and biofilm formation are increased 21390082 IS5 insertion disrupts the H-NS binding site, thus preventing transcriptional repression of the operon 21390082br>In a study where it was shown that the L-tryptophan eradicated persister cells, it was observed that the exogenous amino acid downregulated the expression of flhDC as well as other falgellar genes 31271063.
The mRNA that contains the flhD gene has been observed mainly in the poles of the cell 31540875.
Reference(s): [1] Bertin P., et al., 1994
[3] Shin S., et al., 1995
Promoter
Name: flhDp2
+1: 1978577
Sigma Factor: Sigma54 Sigmulon
Distance from start of the gene: 380
Sequence: aacctgaatctgaggcagcacctggcacggctgggacggaagtcgctgtcgttctcaaaaTcggtggagctgcatgacaaa
                                -24         -12             +1                   
Note(s): This promoter was identified by microarray assays with a mutant σ54 strain and a σ54-overexpressing strain, and by σ54-related promoter element identification Zhao K,2010
We assigned a putative transcription start site to this promoter based on the observation that the majority of the σ54-dependent promoters, whose transcription start sites were determined experimentally, present a distance of 11 nucleotides between the transcription start site and the -12 box Barrios H,1999.
Evidence: [HIPP]
[IEP]
Reference(s): [21] Zhao K., et al., 2010
Terminator(s)
Type: rho-independent
Sequence: ttaacgcgcgATTGGGGCAAAAAAAAGCAGCGGTACGTCGTTACCGCTGCTGGAATGTTGCGCCTcaccgtatca
Reference(s): [7] Feng CQ., et al., 2019
[8] Lesnik EA., et al., 2001
TF binding sites (TFBSs)
[MatA,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd MatA1 repressor flhDp2 nd nd nd nd nd [BPP], [GEA] [2]
Note(s): 1MatA-flhDp2 regulatory interaction was identified in Escherichia coli strain IHE 3034 Lehti TA,2012
MatA binds with higher affinity to flhDp than flhDp2 Lehti TA,20121MatA-flhDp2 regulatory interaction was identified in Escherichia coli strain IHE 3034 Lehti TA,2012
MatA binds with higher affinity to flhDp than flhDp2 Lehti TA,2012


Regulation by sRNA    
  Small RNA name (Regulator) Regulation type Mechanism Function Binding Sites Evidence Reference
LeftPos RightPos Sequence (RNA-strand)
  mcaS     activator      
Notes: "The provided sequence is that of the RNA strand,i.e. 'U's are showed instead the 'T'"


RNA cis-regulatory element    
Regulation, transcriptional elongation  
Attenuator type: Translational
Strand: reverse
  Structure type Energy LeftPos RightPos Sequence (RNA-strand)
  terminator -8.4 1978230 1978246 acatcacgggGTGCGGTGAAACCGCAtaaaaataaa
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    

 [TIM] Transcription initiation mapping

 [APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.

 [CV(GEA)] cross validation(GEA)

 [GEA] Gene expression analysis

 [BPP] Binding of purified proteins

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [CV(SM)] cross validation(SM)

 [SM] Site mutation

 [CV(GEA/SM)] cross validation(GEA/SM)

 [HIPP] Human inference of promoter position

 [IEP] Inferred from expression pattern


Reference(s)    

 [1] Bertin P., Terao E., Lee EH., Lejeune P., Colson C., Danchin A., Collatz E., 1994, The H-NS protein is involved in the biogenesis of flagella in Escherichia coli., J Bacteriol 176(17):5537-40

 [2] Lehti TA., Bauchart P., Dobrindt U., Korhonen TK., Westerlund-Wikstrom B., 2012, The fimbriae activator MatA switches off motility in Escherichia coli by repression of the flagellar master operon flhDC., Microbiology 158(Pt 6):1444-55

 [3] Shin S., Park C., 1995, Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR., J Bacteriol 177(16):4696-702

 [4] Barker CS., Pruss BM., Matsumura P., 2004, Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon., J Bacteriol 186(22):7529-37

 [5] Soutourina O., Kolb A., Krin E., Laurent-Winter C., Rimsky S., Danchin A., Bertin P., 1999, Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon., J Bacteriol 181(24):7500-8

 [6] Wei BL., Brun-Zinkernagel AM., Simecka JW., Pruss BM., Babitzke P., Romeo T., 2001, Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli., Mol Microbiol 40(1):245-56

 [7] Feng CQ., Zhang ZY., Zhu XJ., Lin Y., Chen W., Tang H., Lin H., 2019, iTerm-PseKNC: a sequence-based tool for predicting bacterial transcriptional terminators., Bioinformatics 35(9):1469-1477

 [8] Lesnik EA., Sampath R., Levene HB., Henderson TJ., McNeil JA., Ecker DJ., 2001, Prediction of rho-independent transcriptional terminators in Escherichia coli., Nucleic Acids Res 29(17):3583-94

 [9] Lehnen D., Blumer C., Polen T., Wackwitz B., Wendisch VF., Unden G., 2002, LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli., Mol Microbiol 45(2):521-32

 [10] Amores GR., de Las Heras A., Sanches-Medeiros A., Elfick A., Silva-Rocha R., 2017, Systematic identification of novel regulatory interactions controlling biofilm formation in the bacterium Escherichia coli., Sci Rep 7(1):16768

 [11] Otsuka J., Watanabe H., Mori KT., 1996, Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli., J Theor Biol 178(2):183-204

 [12] Zhao K., Liu M., Burgess RR., 2007, Adaptation in bacterial flagellar and motility systems: from regulon members to 'foraging'-like behavior in E. coli., Nucleic Acids Res 35(13):4441-52

 [13] Kim YJ., Im SY., Lee JO., Kim OB., 2016, Potential Swimming Motility Variation by AcrR in Escherichia coli., J Microbiol Biotechnol 26(10):1824-1828

 [14] Wiebe H., Gurlebeck D., Gross J., Dreck K., Pannen D., Ewers C., Wieler LH., Schnetz K., 2015, YjjQ Represses Transcription of flhDC and Additional Loci in Escherichia coli., J Bacteriol 197(16):2713-20

 [15] Filippova EV., Zemaitaitis B., Aung T., Wolfe AJ., Anderson WF., 2018, Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB., MBio 9(1)

 [16] Francez-Charlot A., Laugel B., Van Gemert A., Dubarry N., Wiorowski F., Castani?-Cornet MP., Gutierrez C., Cam K., 2003, RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli., Mol Microbiol 49(3):823-32

 [17] Pesavento C., Hengge R., 2012, The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity., Nucleic Acids Res 40(11):4783-93

 [18] Stojiljkovic I., Baumler AJ., Hantke K., 1994, Fur regulon in gram-negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a fur titration assay., J Mol Biol 236(2):531-45

 [19] Sperandio V., Torres AG., Kaper JB., 2002, Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli., Mol Microbiol 43(3):809-21

 [20] Ko M., Park C., 2000, H-NS-Dependent regulation of flagellar synthesis is mediated by a LysR family protein., J Bacteriol 182(16):4670-2

 [21] Zhao K., Liu M., Burgess RR., 2010, Promoter and regulon analysis of nitrogen assimilation factor, sigma54, reveal alternative strategy for E. coli MG1655 flagellar biosynthesis., Nucleic Acids Res 38(4):1273-83

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