RegulonDB RegulonDB 10.7: Operon Form
   

hdeAB-yhiD operon and associated TUs in Escherichia coli K-12 genome




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


Transcription unit          
Name: hdeAB-yhiD
Gene(s): yhiD, hdeB, hdeA   Genome Browser M3D Gene expression COLOMBOS
Note(s): The hdeAB-yhiD operon is induced under stationary phase |CITS: [16204188] [15716429]| and at acid pH |CITS: [17026754] [12730179][23274360]| in a RcsB-dependent manner |CITS:[21571995]|.
Lrp represses the hdeAB-yhiD operon only in the exponential phase at pH 7.0, and MarA reduces this repression |CITS: [18083817]|.
Indole enhances the expression of several genes related to acid resistance, such as gadA, gadB, gadC, hdeA, hdeB, hdeD, slp, and gadE |CITS:[20470880]|. The acid resistance phenotype induced by indoles is mainly due to increased expression of the glutamine decarboxylase system |CITS:[20470880]|.
The mdtEF-tolC, malEFG, gadBC, treBC, entCEBA-ybdB, hdeAB-yhiD, and alaE operons were differentially regulated after induction of the nonnative organic acid citramalate |CITS:[31186337]|.
Evidence: [ITC] Inferred through co-regulation
[LTED] Length of transcript experimentally determined
Reference(s): [1] Arnqvist A., et al., 1994
[2] Tucker DL., et al., 2003
[3] Yoshida T., et al., 1993
Promoter
Name: hdeAp
+1: 3656791
Sigma Factor: Sigma38, Sigma70, Sigma70, Sigma38
Distance from start of the gene: 51
Sequence: tctgattttgatattttccatcaacatgacatatacagaaaaccaggttataacctcagtGtcgaaattgattcgtgacgg
                           -35                   -10        +1                   
Note(s): The same transcriptional start site for this promoter is used in hns rpoS mutant strains as well as strains wild type for H-NS and σ38. This indicates that the same promoter can be utilized by both σ38 and σ70 in vivo. This promoter has significant homology to the consensus of a σ70 promoter even though it is dependent upon σ38 Arnqvist A,1994.
Evidence: [HIPP]
[RS-EPT-CBR]
[TIM]
Reference(s): [1] Arnqvist A., et al., 1994
[4] Dudin O., et al., 2013
[5] Itou J., et al., 2009
[6] Salgado H, et al., 2012
TF binding sites (TFBSs)
[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 hdeAp 3656757 3656812 8.0 catatacagaAAACCAGGTTATAACCTCAGTGTCGAAATTGATTCGTGACGGCTCTTTCACTTTATagttgaggat nd [BPP], [GEA] [16]
[GadE,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal GadE activator hdeAp 3656773 3656792 9.5 ataacctcagTGTCGAAATTGATTCGTGACggctctttca nd , [IHBCE], [11]
remote GadE2 activator hdeAp 3656899 3656918 -117.5 aatgcagtcgATTTAATAAAAATTTCCTAAttgcagtatc nd [AIBSCS], [APIORCISFBSCS], [BPP], , [GEA], [IHBCE], [2], [5], [7], [10], [11]
[GadW,+-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal GadW activator hdeAp 3656835 3656854 -53.5 tgaaataaaaATATCTGATTTTGATATTTTccatcaacat nd [AIBSCS], [APIORCISFBSCS], [BPP], [GEA] [2], [7], [12]
proximal GadW repressor hdeAp 3656835 3656854 -53.5 tgaaataaaaATATCTGATTTTGATATTTTccatcaacat nd [AIBSCS], [APIORCISFBSCS], [BPP], [GEA] [2], [7], [12]
proximal GadW repressor hdeAp 3656856 3656875 -74.5 tgcatctgtaACTCATTGTATTGAAATAAAaatatctgat nd [APIORCISFBSCS], [BPP], [GEA] [2], [7], [12]
proximal GadW activator hdeAp 3656856 3656875 -74.5 tgcatctgtaACTCATTGTATTGAAATAAAaatatctgat nd [APIORCISFBSCS], [BPP], [GEA] [2], [7], [12]
remote GadW repressor hdeAp 3656908 3656927 -126.5 gcgtctaagaATGCAGTCGATTTAATAAAAatttcctaat nd [AIBSCS], [GEA] [2], [7]
remote GadW activator hdeAp 3656908 3656927 -126.5 gcgtctaagaATGCAGTCGATTTAATAAAAatttcctaat nd [AIBSCS], [GEA] [2], [7]
[GadX,+-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal GadX1 repressor hdeAp 3656835 3656854 -53.5 tgaaataaaaATATCTGATTTTGATATTTTccatcaacat nd [APIORCISFBSCS], [BPP], [GEA] [2], [7], [10], [12]
proximal GadX2 activator hdeAp 3656835 3656854 -53.5 tgaaataaaaATATCTGATTTTGATATTTTccatcaacat nd [APIORCISFBSCS], [BPP], [GEA] [2], [7], [10], [12]
proximal GadX3 repressor hdeAp 3656856 3656875 -74.5 tgcatctgtaACTCATTGTATTGAAATAAAaatatctgat nd [AIBSCS], [APIORCISFBSCS], [BPP], [GEA] [2], [7], [10], [12]
proximal GadX4 activator hdeAp 3656856 3656875 -74.5 tgcatctgtaACTCATTGTATTGAAATAAAaatatctgat nd [AIBSCS], [APIORCISFBSCS], [BPP], [GEA] [2], [7], [10], [12]
remote GadX activator hdeAp 3656908 3656927 -126.5 gcgtctaagaATGCAGTCGATTTAATAAAAatttcctaat nd [AIBSCS], [GEA] [2], [7]
remote GadX repressor hdeAp 3656908 3656927 -126.5 gcgtctaagaATGCAGTCGATTTAATAAAAatttcctaat nd [AIBSCS], [GEA] [2], [7]
[H-NS,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote H-NS1 repressor hdeAp 3656902 3656916 -118.0 tgcagtcgatTTAATAAAAATTTCCtaattgcagt nd [APIORCISFBSCS], [BPP], [GEA] [3], [8], [9]
[Lrp,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal Lrp-leucine repressor hdeAp 3656802 3656817 -18.0 catgacatatACAGAAAACCAGGTTAtaacctcagt nd [AIBSCS], [GEA] [7]
proximal Lrp-leucine repressor hdeAp 3656839 3656854 -55.0 tgaaataaaaATATCTGATTTTGATAttttccatca nd [AIBSCS], [GEA] [7]
proximal Lrp-leucine repressor hdeAp 3656848 3656863 -64.0 tcattgtattGAAATAAAAATATCTGattttgatat nd [AIBSCS], [GEA] [7]
remote Lrp-leucine repressor hdeAp 3656881 3656896 -97.0 tttcctaattGCAGTATCTGATGCATctgtaactca nd [AIBSCS], [GEA] [7]
remote Lrp-leucine repressor hdeAp 3656900 3656915 -116.0 gcagtcgattTAATAAAAATTTCCTAattgcagtat nd [AIBSCS], [GEA] [7]
remote Lrp-leucine repressor hdeAp 3656943 3656958 -159.0 aaatcccctgCTATCAATCTATGCCAaaaacgcgtc nd [AIBSCS], [GEA] [7]
[MarA,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal MarA1 repressor hdeAp 3656820 3656839 -39.0 tgattttgatATTTTCCATCAACATGACATatacagaaaa nd [APIORCISFBSCS], [APPH], [GEA], [SM] [13]
[PhoP,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal PhoP-Phosphorylated activator hdeAp 3656815 3656831 -32.0 atattttccaTCAACATGACATATACAgaaaaccagg nd [APIORCISFBSCS], [BPP], [GEA] [14]
[RcsB,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
nd RcsB-Pasp56 activator hdeAp nd nd nd nd nd [GEA] [17]
[TorR,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal TorR-Pasp1 activator hdeAp 3656814 3656823 -27.5 catcaacatgACATATACAGaaaaccaggt nd [AIBSCS], [GEA] [7], [15]
proximal TorR-Pasp2 activator hdeAp 3656838 3656847 -51.5 aaaatatctgATTTTGATATtttccatcaa nd [AIBSCS], [GEA] [7]
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.2GadE is the main activator of the hdeAB-yhiD operon. Both H-NS and GadE are involved in increasing the hdeAB-yhiD repression levels by MarA that occur as the cell enters the stationary phase Ruiz C,2008.1GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
2GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
3GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
4GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
1H-NS represses transcription through the binding to supercoiled DNA Yoshida T,1993. H-NS represses the transcription initiation at hdeAp by σ70, but not by σ38. This repression is not through a direct interaction with σ70; instead, it acts as a cofactor for DNA looping. H-NS bound at 118 laterally extends to the promoter downstream sequence and wraps the DNA around σ70 through the cooperative recruitment of other H-NS molecules Shin M,2005.
H-NS is the main repressor of the hdeAB-yhiD operon. Both H-NS and GadE are involved in increasing the hdeAB-yhiD repression levels by MarA that occur as the cell enters the stationary phase Ruiz C,2008.
1MarA plays a very important role in the complex negative regulation of the hdeAB-yhiD operon during the stationary phase and acid resistance that depends on the growth conditions, on other regulators of hdeAB-yhiD expression, and on the degree of induction of marA expression. MarA also controls it, by modifying the effects of the other regulators. This transcriptional regulator binds to a marbox partially overlapping the -35 box of the hdeAp promoter, competing with the RNA polymerase for DNA binding and/or direct interactions between MarA and σ70, σ38, or other subunits of RNA polymerase. In addition, several putative binding sites are located near the marbox . MarA reduces the repression caused by GadX and Lrp during exponential phase and it helps H-NS repression, although it is not clear how. On the other hand, MarA reduces the ability of GadE to activate the hdeAB-yhiD operon during the stationary phase, since they compete for DNA binding or for interacting. This regulator also reduces the repression caused by GadW during stationary phase. Finally, MarA seems to compete functionally with GadX, GadW, RpoS, and Lrp under some conditions, which might ensure that hdeAB-yhiD expression is not repressed more than necessary Ruiz C,2008.1TorR shows no significant effect in the expression of hdeAB-yhiD, which suggests that TorR only regulates the hdeAB-yhiD operon after induction of the TorRS system by trimethylamine, N-oxide, and anaerobiosis Bordi C,2003. Ruiz C,2008. Two predicted sites have been reported Ruiz C,2008.
2TorR shows no significant effect in the expression of hdeAB-yhiD, which suggests that TorR only regulates the hdeAB-yhiD operon after induction of the TorRS system by trimethylamine, N-oxide, and anaerobiosis Bordi C,2003. Ruiz C,2008. Two predicted sites have been reported Ruiz C,2008.6H-NS represses transcription through the binding to supercoiled DNA Yoshida T,1993. H-NS represses the transcription initiation at hdeAp by σ70, but not by σ38. This repression is not through a direct interaction with σ70; instead, it acts as a cofactor for DNA looping. H-NS bound at 118 laterally extends to the promoter downstream sequence and wraps the DNA around σ70 through the cooperative recruitment of other H-NS molecules Shin M,2005.
H-NS is the main repressor of the hdeAB-yhiD operon. Both H-NS and GadE are involved in increasing the hdeAB-yhiD repression levels by MarA that occur as the cell enters the stationary phase Ruiz C,2008.

7GadE is the main activator of the hdeAB-yhiD operon. Both H-NS and GadE are involved in increasing the hdeAB-yhiD repression levels by MarA that occur as the cell enters the stationary phase Ruiz C,2008.
10GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
12GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
17GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
19GadX has a positive direct or indirect effect on the hdeAB-yhiD operon only in stationary-phase cells at pH 5.5, but it is a repressor in exponential growth phase at pH 7.0 Ruiz C,2008.
20TorR shows no significant effect in the expression of hdeAB-yhiD, which suggests that TorR only regulates the hdeAB-yhiD operon after induction of the TorRS system by trimethylamine, N-oxide, and anaerobiosis Bordi C,2003. Ruiz C,2008. Two predicted sites have been reported Ruiz C,2008.
21MarA plays a very important role in the complex negative regulation of the hdeAB-yhiD operon during the stationary phase and acid resistance that depends on the growth conditions, on other regulators of hdeAB-yhiD expression, and on the degree of induction of marA expression. MarA also controls it, by modifying the effects of the other regulators. This transcriptional regulator binds to a marbox partially overlapping the -35 box of the hdeAp promoter, competing with the RNA polymerase for DNA binding and/or direct interactions between MarA and σ70, σ38, or other subunits of RNA polymerase. In addition, several putative binding sites are located near the marbox . MarA reduces the repression caused by GadX and Lrp during exponential phase and it helps H-NS repression, although it is not clear how. On the other hand, MarA reduces the ability of GadE to activate the hdeAB-yhiD operon during the stationary phase, since they compete for DNA binding or for interacting. This regulator also reduces the repression caused by GadW during stationary phase. Finally, MarA seems to compete functionally with GadX, GadW, RpoS, and Lrp under some conditions, which might ensure that hdeAB-yhiD expression is not repressed more than necessary Ruiz C,2008.
23TorR shows no significant effect in the expression of hdeAB-yhiD, which suggests that TorR only regulates the hdeAB-yhiD operon after induction of the TorRS system by trimethylamine, N-oxide, and anaerobiosis Bordi C,2003. Ruiz C,2008. Two predicted sites have been reported Ruiz C,2008.
25No 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.


Transcription unit       
Gene(s): yhiD   Genome Browser M3D Gene expression COLOMBOS
Evidence: [ICWHO] Inferred computationally without human oversight


Regulation by sRNA    
  Small RNA name (Regulator) Regulation type Mechanism Function Binding Sites Evidence Reference
LeftPos RightPos Sequence (RNA-strand)
  gcvB unknown unknown repressor       [IMP] [18]
  oxyS antisense post-transcriptional regulation repressor       [GEA]
[IMP]
[IPI]		 [19]
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: Transcriptional
Strand: reverse
Evidence: [ICA] Inferred by computational analysis
Reference(s): [20] Merino E, et al., 2005
  Structure type Energy LeftPos RightPos Sequence (RNA-strand)
  terminator -17.3 3655903 3655948 caagtaaaaaGGAGTAGCAAGTTGAGCCATCTTGCTGCTCCTTTTTGCATTTTTAtatgacagca
  terminator -8.7 3656300 3656331 agctattcctCCTGTTCATATATAATCTCTATATTGAATGGgttacaaaat
  anti-terminator -9.06 3655933 3656001 tttgtataccTTCAAAAATCAAGCATCTAATGACTTGCCGAATTAATGAGGTGCAAGTAAAAAGGAGTAGCAAGTTGAgccatcttgc
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    

 [HIPP] Human inference of promoter position

 [RS-EPT-CBR] RNA-seq using two enrichment strategies for primary transcripts and consistent biological replicates

 [TIM] Transcription initiation mapping

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [CEUMA] ChIP-exo evidence used in manual assertion

 [IHBCE] Inferred by a human based on computational evidence

 [RE] RNA-seq evidence

 [AIBSCS] Automated inference based on similarity to consensus sequences

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

 [APPH] Assay of protein purified to homogeneity

 [SM] Site mutation


Reference(s)    

 [1] Arnqvist A., Olsen A., Normark S., 1994, Sigma S-dependent growth-phase induction of the csgBA promoter in Escherichia coli can be achieved in vivo by sigma 70 in the absence of the nucleoid-associated protein H-NS., Mol Microbiol 13(6):1021-32

 [2] Tucker DL., Tucker N., Ma Z., Foster JW., Miranda RL., Cohen PS., Conway T., 2003, Genes of the GadX-GadW regulon in Escherichia coli., J Bacteriol 185(10):3190-201

 [3] Yoshida T., Ueguchi C., Yamada H., Mizuno T., 1993, Function of the Escherichia coli nucleoid protein, H-NS: molecular analysis of a subset of proteins whose expression is enhanced in a hns deletion mutant., Mol Gen Genet 237(1-2):113-22

 [4] Dudin O., Lacour S., Geiselmann J., 2013, Expression dynamics of RpoS/Crl-dependent genes in Escherichia coli., Res Microbiol 164(8):838-47

 [5] Itou J., Eguchi Y., Utsumi R., 2009, Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12., Biosci Biotechnol Biochem 73(4):870-8

 [6] Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muñiz-Rascado L, García-Sotelo JS, Weiss V, Solano-Lira H, Martínez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernández S, Alquicira-Hernández K, López-Fuentes A, Porrón-Sotelo L, Huerta AM, Bonavides-Martínez C, Balderas-Martínez YI, Pannier L, Olvera M, Labastida A, Jiménez-Jacinto V, Vega-Alvarado L, Del Moral-Chávez V, Hernández-Alvarez A, Morett E, Collado-Vides J., 2012, RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more., Nucleic Acids Res.

 [7] Ruiz C., McMurry LM., Levy SB., 2008, Role of the multidrug resistance regulator MarA in global regulation of the hdeAB acid resistance operon in Escherichia coli., J Bacteriol 190(4):1290-7

 [8] De Biase D., Tramonti A., Bossa F., Visca P., 1999, The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system., Mol Microbiol 32(6):1198-211

 [9] Shin M., Song M., Rhee JH., Hong Y., Kim YJ., Seok YJ., Ha KS., Jung SH., Choy HE., 2005, DNA looping-mediated repression by histone-like protein H-NS: specific requirement of Esigma70 as a cofactor for looping., Genes Dev 19(19):2388-98

 [10] Hommais F., Krin E., Coppee JY., Lacroix C., Yeramian E., Danchin A., Bertin P., 2004, GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli., Microbiology 150(Pt 1):61-72

 [11] Seo SW., Kim D., O'Brien EJ., Szubin R., Palsson BO., 2015, Decoding genome-wide GadEWX-transcriptional regulatory networks reveals multifaceted cellular responses to acid stress in Escherichia coli., Nat Commun 6:7970

 [12] Tramonti A., De Canio M., De Biase D., 2008, GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites., Mol Microbiol 70(4):965-82

 [13] Schneiders T., Barbosa TM., McMurry LM., Levy SB., 2004, The Escherichia coli transcriptional regulator MarA directly represses transcription of purA and hdeA., J Biol Chem 279(10):9037-42

 [14] Zwir I., Shin D., Kato A., Nishino K., Latifi T., Solomon F., Hare JM., Huang H., Groisman EA., 2005, Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica., Proc Natl Acad Sci U S A 102(8):2862-7

 [15] Bordi C., Theraulaz L., Mejean V., Jourlin-Castelli C., 2003, Anticipating an alkaline stress through the Tor phosphorelay system in Escherichia coli., Mol Microbiol 48(1):211-23

 [16] 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

 [17] Johnson MD., Burton NA., Gutierrez B., Painter K., Lund PA., 2011, RcsB Is Required for Inducible Acid Resistance in Escherichia coli and Acts at gadE-Dependent and -Independent Promoters., J Bacteriol 193(14):3653-6

 [18] Pulvermacher SC., Stauffer LT., Stauffer GV., 2009, Role of the sRNA GcvB in regulation of cycA in Escherichia coli., Microbiology 155(Pt 1):106-14

 [19] Altuvia S, Zhang A, Argaman L, Tiwari A, Storz G, 1998, The Escherichia coli OxyS regulatory RNA represses fhlA translation by blocking ribosome binding., EMBO J, 1998 Oct 15

 [20] Merino E, Yanofsky C., 2005, Transcription attenuation: a highly conserved regulatory strategy used by bacteria., Trends Genet. 2005 May;21(5):260-4.

RegulonDB