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GalR DNA-binding transcriptional dual regulator

Synonyms: GalR-galactose, GalR
Summary:
The Galactose repressor, GalR, is a DNA-binding transcription factor that represses transcription of the operons involved in transport and catabolism of D-galactose |CITS: [17630975][7934815][8416900][8982002]|. Synthesis of these operons is induced when E. coli is grown in the presence of inducer (D-galactose) and the absence glucose |CITS:[8982002][7934815][1619663][8416900]|. The expression of galR is increased only in the presence of inducer |CITS:[8416900][8982002]|.
In particular, in the absence of D-galactose, GalR represses the galETKM operon |CITS:[9218807]|. In this repression system, GalR binds to two operators in the presence of HU, resulting in the formation of a repressor loop |CITS:[9218807][12169637][15289461]|. This repressor binds in tandem to inverted repeat sequences that are 16 nucleotides long and possess conserved motifs; each dimer binds to one of these conserved sequences |CITS:[7934815][8416900]|.
On the other hand, GalR is highly homologous in its amino acid sequence to GalS (55% identical and 88% similar); apparently both act together and are capable of cross-talk to regulate expression of the gal regulon |CITS:[1619663][8982002]|. For this reason these regulators bind the same operators, in the cis regulatory regions, with different affinities |CITS:[8175668]|. In the presence of inductor, GalR undergoes a conformational change that reduces its affinity for the operator. Golding et al. showed that GalR is the major repressor of the gal operon |CITS:[1655705]|.
GalR belongs to the GalR/LacI family of transcriptional regulators.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
GalR Functional   Apo [BPP], [GEA], [IDA], [IPI] [1], [2]
GalR-galactose Non-Functional Allosteric Holo [BPP], [GEA], [IDA], [IPI] [1], [2]
Evolutionary Family: GalR/LacI
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: galR
  Genome position: 2976599-2977630
  Length: 1032 bp / 343 aa
Operon name: galR
TU(s) encoding the TF:
Transcription unit        Promoter
galR
galRp


Regulon       
Regulated gene(s) galE, galK, galM, galP, galR, galS, galT, mglA, mglB, mglC
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (10)
colanic acid (M antigen) (3)
galactose metabolism (3)
capsule (M and K antigens) (3)
membrane (2)
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Regulated operon(s) galETKM, galP, galR, galS, mglBAC
First gene in the operon(s) galE, galE, galE, galE, galE, galE, galE, galE, galP, galR, galS, mglB
Simple and complex regulons CRP,FlhDC,GalR,GalS
CRP,GalR,GalS
CRP,GalR,GalS,H-NS,HU
CRP,GalR,GalS,HU
CRP,GalR,GalS,NagC
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[GalR,-](6)
[GalR,+-](1)


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
  GalR repressor galEp1 Sigma70 -60.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
792134 792149 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]
  GalR repressor galEp1 Sigma70 46.5 19.5 galE, galT, galK, galM
gagagttctgGTTACCGGTGGTAGCGgttacattgg
792028 792043 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]
  GalR repressor galEp2 Sigma70 -55.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
792134 792149 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]
  GalR-galactose activator galEp2 Sigma70 -55.5 -86.5 galE, galT, galK, galM
ctaaattcttGTGTAAACGATTCCACtaatttattc
792134 792149 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13]
  GalR repressor galEp2 Sigma70 51.5 19.5 galE, galT, galK, galM
gagagttctgGTTACCGGTGGTAGCGgttacattgg
792028 792043 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]
  GalR-galactose repressor galPp Sigma70 -243.5 -272.5 galP
atcatcacaaCTGAAACCGATTACACcaaccacaac
3088004 3088019 [AIBSCS], [BPP], [SM] [16]
  GalR-galactose repressor galPp Sigma70 -207.5 -236.5 galP
agacaaagatTTGTAATATTTTCATAttattattcg
3088040 3088055 [BPP] [16]
  GalR-galactose repressor galPp Sigma70 -178.5 -207.5 galP
ttattcggttTTCACAGTTGTTACATttcttttcag
3088069 3088084 [AIBSCS], [BPP], [SM] [16]
  GalR-galactose repressor galPp Sigma70 -107.5 -136.5 galP
tgatgatataACTCAATTATTTTCATgcacttaaat
3088140 3088155 [AIBSCS], [BPP], [SM] [16]
  GalR repressor galPp Sigma70 -61.5 -90.5 galP
ataaatgttaGTGTAAGCGATTACACtgatgtgatt
3088186 3088201 [BPP], [GEA], [HIBSCS], [SM] [1], [9], [13], [16]
  GalR repressor galPp Sigma70 136.5 106.5 galP
cctggatatcGGTGTAATTGCTGGCGcactgccgtt
3088383 3088398 [BPP], [GEA], [HIBSCS], [SM] [1], [9], [13], [16]
  GalR-galactose repressor galRp Sigma70 8.5 -22.5 galR
cactgaaagaATGTAAGCGTTTACCCactaaggtat
2976569 2976584 [BPP], [GEA], [HIBSCS] [2], [9]
  GalR repressor galSp Sigma70 -61.5 -103.5 galS
aacaaaacggCTGTAACCGTTTCCATtgctgtgact
2241764 2241779 [GEA], [HIBSCS] [2], [13]
  GalR repressor galSp Sigma70 91.5 48.5 galS
ctggcgtctcTGTGGCAACGGTTTCCcgggtgctca
2241612 2241627 [GEA], [HIBSCS] [2], [9], [13]
  GalR repressor mglBp Sigma70 -59.5 -277.5 mglB, mglA, mglC
aaatcaggcgATGTAACCGCTTTCAAtctgtgagtg
2240618 2240633 [GEA], [HIBSCS] [1], [9], [13]


Alignment and PSSM for GalR TFBSs    

Aligned TFBS of GalR   
  Sequence
 

Position weight matrix (PWM).   
A	0	4	12	12	4	1	3	3	0	2	3	2	10	3	3
C	0	0	0	0	6	8	0	6	0	0	5	9	0	6	2
G	12	0	0	0	0	0	9	0	0	3	2	1	2	0	0
T	0	8	0	0	2	3	0	3	12	7	2	0	0	3	7

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

 [SM] Site mutation

 [AIBSCS] Automated inference based on similarity to consensus sequences



Reference(s)    

 [1] Geanacopoulos M., Adhya S., 1997, Functional characterization of roles of GalR and GalS as regulators of the gal regulon., J Bacteriol. 179(1):228-34

 [2] Weickert MJ., Adhya S., 1993, Control of transcription of gal repressor and isorepressor genes in Escherichia coli., J Bacteriol. 175(1):251-8

 [3] Choy HE., Hanger RR., Aki T., Mahoney M., Murakami K., Ishihama A., Adhya S., 1997, Repression and activation of promoter-bound RNA polymerase activity by Gal repressor., J Mol Biol. 272(3):293-300

 [4] Kar S., Adhya S., 2001, Recruitment of HU by piggyback: a special role of GalR in repressosome assembly., Genes Dev. 15(17):2273-81

 [5] Lia G., Bensimon D., Croquette V., Allemand JF., Dunlap D., Lewis DE., Adhya S., Finzi L., 2003, Supercoiling and denaturation in Gal repressor/heat unstable nucleoid protein (HU)-mediated DNA looping., Proc Natl Acad Sci U S A. 100(20):11373-7

 [6] Lyubchenko YL., Shlyakhtenko LS., Aki T., Adhya S., 1997, Atomic force microscopic demonstration of DNA looping by GalR and HU., Nucleic Acids Res. 25(4):873-6

 [7] Mandal N., Su W., Haber R., Adhya S., Echols H., 1990, DNA looping in cellular repression of transcription of the galactose operon., Genes Dev. 4(3):410-8

 [8] Perez N., Rehault M., Amouyal M., 2000, A functional assay in Escherichia coli to detect non-assisted interaction between galactose repressor dimers., Nucleic Acids Res. 28(18):3600-4

 [9] Semsey S., Krishna S., Sneppen K., Adhya S., 2007, Signal integration in the galactose network of Escherichia coli., Mol Microbiol. 65(2):465-76

 [10] Semsey S., Tolstorukov MY., Virnik K., Zhurkin VB., Adhya S., 2004, DNA trajectory in the Gal repressosome., Genes Dev. 18(15):1898-907

 [11] Virnik K., Lyubchenko YL., Karymov MA., Dahlgren P., Tolstorukov MY., Semsey S., Zhurkin VB., Adhya S., 2003, Antiparallel DNA loop in gal repressosome visualized by atomic force microscopy., J Mol Biol. 334(1):53-63

 [12] Weickert MJ., Adhya S., 1992, Isorepressor of the gal regulon in Escherichia coli., J Mol Biol. 226(1):69-83

 [13] Weickert MJ., Adhya S., 1993, The galactose regulon of Escherichia coli., Mol Microbiol. 10(2):245-51

 [14] Lewis DE., Geanacopoulos M., Adhya S., 1999, Role of HU and DNA supercoiling in transcription repression: specialized nucleoprotein repression complex at gal promoters in Escherichia coli., Mol Microbiol. 31(2):451-61

 [15] Semsey S., Geanacopoulos M., Lewis DE., Adhya S., 2002, Operator-bound GalR dimers close DNA loops by direct interaction: tetramerization and inducer binding., EMBO J. 21(16):4349-56

 [16] El Qaidi S., Allemand F., Oberto J., Plumbridge J., 2008, Repression of galP, the galactose transporter in Escherichia coli, requires the specific regulator of N-acetylglucosamine metabolism., Mol Microbiol



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