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IclR DNA-binding transcriptional repressor

Synonyms: IclR-pyruvate, IclR-glyoxylate, IclR
Summary:
The transcription factor IclR, for "Isocitrate lyase Regulator," is negatively autoregulated [5]and it regulates the expression of the glyoxylate bypass operon [4, 6, 7, 8, 9, 10] Transcription of this operon is induced when E. coli is grown during acetate accumulation in the exponential phase. Glyoxylate and pyruvate have been identified as effectors of IclR and show antagonistic effects. While glyoxylate favors the inactive dimeric state of IclR, pyruvate increases the binding of IclR to the aceBp promoter by stabilizing the active tetrameric form of the protein [11] On other hand, the genes of the aceBAK operon are expressed to varied degrees due to two facts: first, they are differentially regulated at the translational level, and second, there is a putative premature transcriptional termination in the region preceding the aceK gene [12] IclR represses aceBAK transcription through two mechanisms [1] (1) binding to the proximal site, overlapping the -35 promoter box, and preventing RNA polymerase binding [2, 4, 13] and (2) binding to the distal site after the RNA polymerase has bound to the promoter and formed the open complex, avoiding the polymerase escape of the promoter through its interaction with the α-subunits.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence Confidence level (C: Confirmed, S: Strong, W: Weak) References
IclR Non-Functional   Apo nd nd nd
IclR-glyoxylate Non-Functional Allosteric Holo nd nd nd
IclR-pyruvate Functional Allosteric Holo nd nd nd
Evolutionary Family: IclR
TFBs length: 7
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: iclR
  Genome position: 4222804-4223628
  Length: 825 bp / 274 aa
Operon name: iclR
TU(s) encoding the TF:
Transcription unit        Promoter
iclR
iclRp


Regulon       
Regulated gene(s) aceA, aceB, aceK, iclR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
glyoxylate bypass (4)
posttranslational modification (1)
covalent modification, demodification, maturation (1)
Transcription related (1)
repressor (1)
Regulated operon(s) aceBAK, iclR
First gene in the operon(s) aceB, iclR
Simple and complex regulons ArcA,CRP,Cra,IHF,IclR
FadR,IclR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[IclR,-](2)


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 Confidence level (C: Confirmed, S: Strong, W: Weak) References
  IclR-pyruvate repressor aceBp Sigma70 -141.0 -217.0 aceB, aceA, aceK
tacctcaggcACCTTCGggtgcctttt
 4215258 4215264 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  IclR-pyruvate repressor aceBp Sigma70 -131.0 -207.0 aceB, aceA, aceK
accttcgggtGCCTTTTttatttccga
 4215268 4215274 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  IclR-pyruvate repressor aceBp Sigma70 -122.0 -198.0 aceB, aceA, aceK
tgccttttttATTTCCGaaacgtacct
 4215277 4215283 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  IclR-pyruvate repressor aceBp Sigma70 -104.0 -180.0 aceB, aceA, aceK
aacgtacctcAGCAGGTgaataaattt
 4215295 4215301 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [1], [1]
  IclR-pyruvate repressor aceBp Sigma70 -53.0 -129.0 aceB, aceA, aceK
atcaagtattTTTAATTaaaatggaaa
 4215346 4215352 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3]
  IclR-pyruvate repressor aceBp Sigma70 -38.0 -114.0 aceB, aceA, aceK
ttaattaaaaTGGAAATTGTTTTTGAttttgcattt
 4215357 4215372 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3]
  IclR-pyruvate repressor aceBp Sigma70 -26.0 -102.0 aceB, aceA, aceK
ttgtttttgaTTTTGCAttttaaatga
 4215373 4215379 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3], [4]
  IclR-pyruvate repressor iclRp nd -7.0 -31.0 iclR
aacaataaaaATGAAAATGATTTCCAcgatacagaa
 4223652 4223667 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [3]


Alignment and PSSM for IclR TFBSs    

Aligned TFBS of IclR   
  Sequence
  AAACAATTTCCATTTT
  AATCATTTTCATTTTT
  AGGCACCTTCGGGTGC
  ATTCACCTGCTGAGGT
  TTTGATTTTGCATTTT
  TTTTTATTTCCGAAAC
  TTTTAATTAAAAATAC
  GGGTGCCTTTTTTATT

Position weight matrix (PWM). IclR matrix-quality result    
A	4	2	1	0	6	3	0	0	1	1	2	3	3	2	2	0
C	0	0	0	4	0	3	3	0	0	5	3	0	0	0	0	3
G	1	2	2	1	1	0	0	0	1	1	1	3	1	1	2	0
T	3	4	5	3	1	2	5	8	6	1	2	2	4	5	4	5

Consensus    
;	consensus.strict             	attcactTtCcgtttt
;	consensus.strict.rc          	AAAACGGAAAGTGAAT
;	consensus.IUPAC              	wkkyamyTtCcrwtky
;	consensus.IUPAC.rc           	RMAWYGGAARKTRMMW
;	consensus.regexp             	[at][gt][gt][ct]a[ac][ct]TtCc[ag][at]t[gt][ct]
;	consensus.regexp.rc          	[AG][AC]A[AT][CT]GGAA[AG][GT]T[AG][AC][AC][AT]

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


Evidence    

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

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

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

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


Reference(s)    

 [1] Yamamoto K., Ishihama A., 2003, Two different modes of transcription repression of the Escherichia coli acetate operon by IclR., Mol Microbiol 47(1):183-94

 [2] Pan B., Unnikrishnan I., LaPorte DC., 1996, The binding site of the IclR repressor protein overlaps the promoter of aceBAK., J Bacteriol 178(13):3982-4

 [3] Baumgart LA, Lee JE, Salamov A, Dilworth DJ, Na H, Mingay M, Blow MJ, Zhang Y, Yoshinaga Y, Daum CG, O'Malley RC, 2021, Persistence and plasticity in bacterial gene regulation., Nat Methods, 18(12):1499 10.1038/s41592-021-01312-2

 [4] Cortay JC., Negre D., Galinier A., Duclos B., Perriere G., Cozzone AJ., 1991, Regulation of the acetate operon in Escherichia coli: purification and functional characterization of the IclR repressor., EMBO J 10(3):675-9

 [5] Gui L., Sunnarborg A., Pan B., LaPorte DC., 1996, Autoregulation of iclR, the gene encoding the repressor of the glyoxylate bypass operon., J Bacteriol 178(1):321-4

 [6] Peskov K, Goryanin I, Prank K, Tobin F, Demin O, 2008, Kinetic modeling of ace operon genetic regulation in Escherichia coli., J Bioinform Comput Biol, 6(5):933 10.1142/s0219720008003771

 [7] Resnik E., Pan B., Ramani N., Freundlich M., LaPorte DC., 1996, Integration host factor amplifies the induction of the aceBAK operon of Escherichia coli by relieving IclR repression., J Bacteriol 178(9):2715-7

 [8] Galinier A., Bleicher F., Negre D., Perriere G., Duclos B., Cozzone AJ., Cortay JC., 1991, Primary structure of the intergenic region between aceK and iclR in the Escherichia coli chromosome., Gene 97(1):149-50

 [9] Cortay JC, Bleicher F, Duclos B, Cenatiempo Y, Gautier C, Prato JL, Cozzone AJ, 1989, Utilization of acetate in Escherichia coli: structural organization and differential expression of the ace operon., Biochimie, 71(9-10):1043 10.1016/0300-9084(89)90109-0

 [10] Maloy SR., Nunn WD., 1982, Genetic regulation of the glyoxylate shunt in Escherichia coli K-12., J Bacteriol 149(1):173-80

 [11] Lorca GL, Ezersky A, Lunin VV, Walker JR, Altamentova S, Evdokimova E, Vedadi M, Bochkarev A, Savchenko A, 2007, Glyoxylate and pyruvate are antagonistic effectors of the Escherichia coli IclR transcriptional regulator., J Biol Chem, 282(22):16476 10.1074/jbc.M610838200

 [12] Cozzone AJ, El-Mansi M, 2005, Control of isocitrate dehydrogenase catalytic activity by protein phosphorylation in Escherichia coli., J Mol Microbiol Biotechnol, 9(3-4):132 10.1159/000089642

 [13] Negre D., Cortay JC., Galinier A., Sauve P., Cozzone AJ., 1992, Specific interactions between the IclR repressor of the acetate operon of Escherichia coli and its operator., J Mol Biol 228(1):23-9

 [14] Sunnarborg A., Klumpp D., Chung T., LaPorte DC., 1990, Regulation of the glyoxylate bypass operon: cloning and characterization of iclR., J Bacteriol 172(5):2642-9

 [15] Donald LJ, Chernushevich IV, Zhou J, Verentchikov A, Poppe-Schriemer N, Hosfield DJ, Westmore JB, Ens W, Duckworth HW, Standing KG, 1996, Preparation and properties of pure, full-length IclR protein of Escherichia coli. Use of time-of-flight mass spectrometry to investigate the problems encountered., Protein Sci, 5(8):1613 10.1002/pro.5560050815

 [16] Negre D., Cortay JC., Old IG., Galinier A., Richaud C., Saint Girons I., Cozzone AJ., 1991, Overproduction and characterization of the iclR gene product of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2., Gene 97(1):29-37

 [17] Lin H, Bennett GN, San KY, 2005, Genetic reconstruction of the aerobic central metabolism in Escherichia coli for the absolute aerobic production of succinate., Biotechnol Bioeng, 89(2):148 10.1002/bit.20298

 [18] Sánchez AM, Bennett GN, San KY, 2005, Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity., Metab Eng, 7(3):229 10.1016/j.ymben.2005.03.001

 [19] Waegeman H, Beauprez J, Moens H, Maertens J, De Mey M, Foulquié-Moreno MR, Heijnen JJ, Charlier D, Soetaert W, 2011, Effect of iclR and arcA knockouts on biomass formation and metabolic fluxes in Escherichia coli K12 and its implications on understanding the metabolism of Escherichia coli BL21 (DE3)., BMC Microbiol, 11(None):70 10.1186/1471-2180-11-70

 [20] Yang J, Fang Y, Wang J, Wang C, Zhao L, Wang X, 2019, Deletion of regulator-encoding genes fadR, fabR and iclR to increase L-threonine production in Escherichia coli., Appl Microbiol Biotechnol, 103(11):4549 10.1007/s00253-019-09818-8

 [21] Shimada T, Nakazawa K, Tachikawa T, Saito N, Niwa T, Taguchi H, Tanaka K, 2021, Acetate overflow metabolism regulates a major metabolic shift after glucose depletion in Escherichia coli., FEBS Lett, 595(15):2047 10.1002/1873-3468.14151

 [22] zhou Y, Huang H, Zhou P, Xie J, 2012, Molecular mechanisms underlying the function diversity of transcriptional factor IclR family., Cell Signal, 24(6):1270 10.1016/j.cellsig.2012.02.008


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