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IclR DNA-binding transcriptional repressor

Synonyms: IclR-pyruvate, IclR-glyoxylate
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 [1]
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 [11]

IclR represses aceBAK transcription through two mechanisms [2] (1) binding to the proximal site, overlapping the -35 promoter box, and preventing RNA polymerase binding [3, 4, 12] 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 (Confirmed, Strong, Weak) References
IclR-glyoxylate Non-Functional Allosteric Holo [BPP], [GEA], [IDA], [IPI] [1]
IclR-pyruvate Functional Allosteric Holo [BPP], [GEA], [IDA], [IPI] [1]
Evolutionary Family: IclR
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 binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence
LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  IclR-pyruvate repressor aceBp Sigma70 -141.0 -217.0 aceB, aceA, aceK
tacctcaggcACCTTCGggtgcctttt
4215258 4215264 [BPP], [GEA], [HIBSCS] [2]
  IclR-pyruvate repressor aceBp Sigma70 -131.0 -207.0 aceB, aceA, aceK
accttcgggtGCCTTTTttatttccga
4215268 4215274 [BPP], [GEA], [HIBSCS] [2]
  IclR-pyruvate repressor aceBp Sigma70 -122.0 -198.0 aceB, aceA, aceK
tgccttttttATTTCCGaaacgtacct
4215277 4215283 [BPP], [GEA], [HIBSCS] [2]
  IclR-pyruvate repressor aceBp Sigma70 -104.0 -180.0 aceB, aceA, aceK
aacgtacctcAGCAGGTgaataaattt
4215295 4215301 [BPP], [GEA], [HIBSCS] [2]
  IclR-pyruvate repressor aceBp Sigma70 -53.0 -129.0 aceB, aceA, aceK
atcaagtattTTTAATTaaaatggaaa
4215346 4215352 [BPP], [GEA], [HIBSCS] [2], [3]
  IclR-pyruvate repressor aceBp Sigma70 -38.0 -114.0 aceB, aceA, aceK
ttaattaaaaTGGAAATTGTTTTTGattttgcatt
4215357 4215371 [BPP], [GEA], [HIBSCS] [2], [3]
  IclR-pyruvate repressor aceBp Sigma70 -26.0 -102.0 aceB, aceA, aceK
ttgtttttgaTTTTGCAttttaaatga
4215373 4215379 [BPP], [GEA], [HIBSCS] [2], [3], [4]
  IclR-pyruvate repressor iclRp nd -7.0 -31.0 iclR
acaataaaaaTGAAAATGATTTCCAcgatacagaa
4223652 4223666 [BPP], [GEA], [HIBSCS] [2], [3]


Alignment and PSSM for IclR TFBSs    

Aligned TFBS of IclR   
  Sequence
  CAGGCACCTTC
  GTGCCTTTTTT
  TTTTTATTTCC
  TATTCACCTGC
  TTTTTAATTAA
  TTTCCATTTTA
  TTTGCATTTTA
  TTTTCATTTTT

Position weight matrix (PWM).   
A	0	2	0	0	0	7	1	0	0	1	3
C	1	0	0	2	6	0	2	2	0	1	3
G	1	0	2	2	0	0	0	0	0	1	0
T	6	6	6	4	2	1	5	6	8	5	2

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    

 [BPP] Binding of purified proteins

 [GEA] Gene expression analysis

 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [HIBSCS] Human inference based on similarity to consensus sequences



Reference(s)    

 [1] 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):16476-91

 [2] 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

 [3] 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

 [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):933-59

 [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):1043-1049

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

 [11] 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):132-46

 [12] 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

 [13] 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

 [14] 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):1613-24

 [15] 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

 [16] 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):148-56

 [17] Sanchez 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):229-39

 [18] zhou Y., Huang H., Zhou P., Xie J., 2012, Molecular mechanisms underlying the function diversity of transcriptional factor IclR family., Cell Signal. 24(6):1270-5



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