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AraC DNA-binding transcriptional dual regulator

Synonyms: AraC-D-fucose, AraC-L-arabinose, AraC
Summary:
The arabinose regulator, AraC, is a transcription factor that regulates transcription of several genes and operons involved in arabinose catabolism and transport. It coregulates with another transcriptional regulator, CRP; both are transcription factors involved in l-arabinose degradation. These regulators bind cooperatively to activate transcription of five operons related to transport, catabolism, and autoregulation of l-arabinose. Transcription of these operons is induced when E. coli is grown in the absence of glucose and when the physiological inducer, l-arabinose, binds to the AraC regulator. In the absence of glucose, cellular cyclic AMP levels are high and cyclic AMP forms a dimeric complex with CRP to coregulate with AraC [9, 12, 18, 19, 22, 25, 26]
AraC binds to five target sites in the araBp region. AraC binds to the less-conserved site (-42.5) with less strength; this binding occurs only in the presence of arabinose, and it is absolutely required for expression of araBp [6, 27, 28, 29, 30] AraC binding to the distal site (-123.5) has been shown to down-regulate expression of araBp and araCp [5, 28]
In the absence of arabinose, AraC is unable to activate araBp, but it regulates its own expression by repressing araCp and araBp simultaneously [27, 28, 29] Arabinose triggers AraC-dependent activation of araBp and relieves AraC-dependent repression of araCp [28, 29] The araBAD operon is located upstream of araC and in the opposite direction.
In the presence of arabinose, this regulator activates transcription by overlapping the -35 box of the core promoters, and the central position of the binding site is located near bp -41.5.
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
AraC Functional   Apo [BPP], [IDA], [IPI], [SM] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]
AraC-D-fucose Non-Functional Allosteric Holo [IPI] [8], [11]
AraC-L-arabinose Functional Allosteric Holo [BPP], [IDA], [IPI], [SM] [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]
Evolutionary Family: AraC/XylS
Sensing class: Sensing external and internal signals
Connectivity class: Local Regulator
Gene name: araC
  Genome position: 70387-71265
  Length: 879 bp / 292 aa
Operon name: araC
TU(s) encoding the TF:
Transcription unit        Promoter
araC
araCp


Regulon       
Regulated gene(s) araA, araB, araC, araD, araE, araF, araG, araH, araJ, xylA, xylB, ydeM, ydeN, ygeA
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
carbon compounds (11)
membrane (3)
Porters (Uni-, Sym- and Antiporters) (2)
Transcription related (1)
activator (1)
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Regulated operon(s) araBAD, araC, araE-ygeA, araFGH, araJ, xylAB, ydeNM
First gene in the operon(s) araB, araC, araE, araE, araF, araJ, xylA, ydeN
Simple and complex regulons AraC,CRP
AraC,CRP,XylR
AraC,NagC
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[AraC,-](3)
[AraC,+](5)
[AraC,+-](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
  AraC repressor araBp Sigma70 -275.0 -302.0 araB, araA, araD
attcagagaaGAAACCAATTGTCCATAttgcatcaga
 70342 70358 [BCE], [BPP], [HIBSCS], [SM] [2], [9], [12], [13], [14], [15], [16]
  AraC-L-arabinose repressor araBp Sigma70 -138.0 -165.0 araB, araA, araD
caaaaacgcgTAACAAAAGTGTCTATAatcacggcag
 70205 70221 [BCE], [GEA], [HIBSCS], [SM] [5], [12], [14]
  AraC-L-arabinose repressor araBp Sigma70 -117.0 -144.0 araB, araA, araD
tctataatcaCGGCAGAAAAGTCCACAttgattattt
 70184 70200 [BCE], [GEA], [HIBSCS], [SM] [5], [12], [14]
  AraC repressor araBp Sigma70 -64.0 -91.0 araB, araA, araD
tgctatgccaTAGCATTTTTATCCATAagattagcgg
 70131 70147 [BPP], [GEA], [HIBSCS], [SM] [1], [9], [12], [13], [14], [15], [16], [17]
  AraC-L-arabinose activator araBp Sigma70 -64.0 -91.0 araB, araA, araD
tgctatgccaTAGCATTTTTATCCATAagattagcgg
 70131 70147 [BPP], [GEA], [HIBSCS], [SM] [1], [9], [12], [13], [14], [15], [16], [17]
  AraC-L-arabinose activator araBp Sigma70 -43.0 -70.0 araB, araA, araD
tccataagatTAGCGGATCCTACCTGAcgctttttat
 70110 70126 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [6], [9], [12], [15], [16], [17]
  AraC-L-arabinose activator araCp Sigma70 -123.0 -269.0 araC
ataaaaagcgTCAGGTAGGATCCGCTAatcttatgga
 70110 70126 [BPP], [GEA], [HIBSCS], [SM] [1], [2], [6], [12], [16], [17]
  AraC repressor araCp Sigma70 -102.0 -248.0 araC
ccgctaatctTATGGATAAAAATGCTAtggcatagca
 70131 70147 [BPP], [GEA], [HIBSCS], [SM] [1], [12], [13], [14], [16], [17]
  AraC-L-arabinose activator araCp Sigma70 -102.0 -248.0 araC
ccgctaatctTATGGATAAAAATGCTAtggcatagca
 70131 70147 [BPP], [GEA], [HIBSCS], [SM] [1], [12], [13], [14], [16], [17]
  AraC-L-arabinose repressor araCp Sigma70 -49.0 -195.0 araC
aaataatcaaTGTGGACTTTTCTGCCGtgattataga
 70184 70200 [BCE], [GEA], [HIBSCS], [SM] [5], [12], [14]
  AraC-L-arabinose repressor araCp Sigma70 -28.0 -174.0 araC
ctgccgtgatTATAGACACTTTTGTTAcgcgtttttg
 70205 70221 [BCE], [GEA], [HIBSCS], [SM] [5], [12], [14]
  AraC repressor araCp Sigma70 110.0 -37.0 araC
tctgatgcaaTATGGACAATTGGTTTCttctctgaat
 70342 70358 [BCE], [BPP], [HIBSCS], [SM] [2], [9], [12], [13], [14], [16]
  AraC-L-arabinose activator araEp Sigma70 -65.0 -91.0 araE, ygeA
cgacatgtcgCAGCAATTTAATCCATAtttatgctgt
 2982265 2982281 [BPP], [HIBSCS] [12], [18]
  AraC-L-arabinose activator araEp Sigma70 -44.0 -70.0 araE, ygeA
tccatatttaTGCTGTTTCCGACCTGAcacctgcgtg
 2982244 2982260 [BPP], [HIBSCS] [12], [18]
  AraC-L-arabinose activator araFp Sigma70 -166.0 -276.0 araF, araG, araH
ccaaagacaaCAAGGATTTCCAGGCTAatcttatgga
 1986396 1986412 [BPP], [SM] [12], [19], [20]
  AraC-L-arabinose activator araFp Sigma70 -145.0 -255.0 araF, araG, araH
aggctaatctTATGGATTAATCTGCTGtgcattcgac
 1986375 1986391 [AIBSCS], [BPP], [HIBSCS] [3], [12], [19], [20]
  AraC-L-arabinose activator araFp Sigma70 -91.0 -201.0 araF, araG, araH
ggctttccctTATGTCTTTTCCCGCTAaatttatgca
 1986321 1986337 [BPP], [SM] [12], [19], [20]
  AraC-L-arabinose activator araFp Sigma70 -70.0 -180.0 araF, araG, araH
ccgctaaattTATGCACGTTCTCACTGtaattctgcg
 1986300 1986316 [BPP], [HIBSCS] [3], [19], [20], [21]
  AraC-L-arabinose activator araJp Sigma70 -64.0 -112.0 araJ
aataactattCAGCAGGATAATGAATAcagaggggcg
 412585 412601 [BPP], [HIBSCS] [12], [19], [22]
  AraC-L-arabinose activator araJp Sigma70 -43.0 -91.0 araJ
tgaatacagaGGGGCGAATTATCTCTTggccttgctg
 412564 412580 [AIBSCS], [BPP] [12], [19], [22]
  AraC-L-arabinose repressor xylAp nd -48.0 -90.0 xylA, xylB
attatctcaaTAGCAGTGTGAAATAACataattgagc
 3730847 3730863 [BCE], [GEA], [HIBSCS] [23]
  AraC-L-arabinose repressor xylAp nd -25.0 -67.0 xylA, xylB
taacataattGAGCAACTGAAAGGGAGtgcccaatat
 3730824 3730840 [BCE], [GEA] [23]
  AraC-L-arabinose repressor ydeNp Sigma70 nd nd ydeN, ydeM
nd
 nd nd [GEA] [24]


Alignment and PSSM for AraC TFBSs    

Aligned TFBS of AraC   
  Sequence
  TCAGGTAGGATCCGCTA
  TATGGATAAAAATGCTA
  TGTGGACTTTTCTGCCG
  TATAGACACTTTTGTTA
  TATGGACAATTGGTTTC
  CAAGAGATAATTCGCCC
  TATTCATTATCCTGCTG
  TATGCACGTTCTCACTG
  TATGTCTTTTCCCGCTA
  TATGGATTAATCTGCTG
  CAAGGATTTCCAGGCTA
  TATGCTGTTTCCGACCT
  TATGGATTAAATTGCTG
  ACTGAAAGGGAGTGCCC
  TATGTTATTTCACACTG

Position weight matrix (PWM).    
A	1	12	3	1	2	10	4	3	6	5	3	3	0	3	0	0	5
C	2	2	0	0	3	1	4	0	1	1	6	6	5	0	13	4	3
G	0	1	0	13	8	1	1	3	2	1	0	2	3	11	0	0	6
T	12	0	12	1	2	3	6	9	6	8	6	4	7	1	2	11	1

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

 [IDA] Inferred from direct assay

 [IPI] Inferred from physical interaction

 [SM] Site mutation

 [BCE] Binding of cellular extracts

 [HIBSCS] Human inference based on similarity to consensus sequences

 [GEA] Gene expression analysis

 [AIBSCS] Automated inference based on similarity to consensus sequences


Reference(s)    

 [1] Bustos SA., Schleif RF., 1993, Functional domains of the AraC protein., Proc Natl Acad Sci U S A. 90(12):5638-42

 [2] Huo L., Martin KJ., Schleif R., 1988, Alternative DNA loops regulate the arabinose operon in Escherichia coli., Proc Natl Acad Sci U S A. 85(15):5444-8

 [3] Johnson CM., Schleif RF., 1995, In vivo induction kinetics of the arabinose promoters in Escherichia coli., J Bacteriol. 177(12):3438-42

 [4] LaRonde-LeBlanc N, Wolberger C., 2000, Characterization of the oligomeric states of wild type and mutant AraC., Biochemistry.

 [5] Lee DH., Huo L., Schleif R., 1992, Repression of the araBAD promoter from araO1., J Mol Biol. 224(2):335-41

 [6] Lee N., Francklyn C., Hamilton EP., 1987, Arabinose-induced binding of AraC protein to araI2 activates the araBAD operon promoter., Proc Natl Acad Sci U S A. 84(24):8814-8

 [7] Rodgers ME., Schleif R., 2009, Solution structure of the DNA binding domain of AraC protein., Proteins. 77(1):202-8

 [8] Ross JJ, Gryczynski U, Schleif R., 2003, Mutational analysis of residue roles in AraC function., J Mol Biol.

 [9] Seabold RR., Schleif RF., 1998, Apo-AraC actively seeks to loop., J Mol Biol. 278(3):529-38

 [10] Soisson SM., MacDougall-Shackleton B., Schleif R., Wolberger C., 1997, Structural basis for ligand-regulated oligomerization of AraC., Science. 276(5311):421-5

 [11] Weldon JE, Rodgers ME, Larkin C, Schleif RF., 2007, Structure and properties of a truely apo form of AraC dimerization domain., Proteins

 [12] Gallegos MT., Schleif R., Bairoch A., Hofmann K., Ramos JL., 1997, Arac/XylS family of transcriptional regulators., Microbiol Mol Biol Rev. 61(4):393-410

 [13] Lee DH., Schleif RF., 1989, In vivo DNA loops in araCBAD: size limits and helical repeat., Proc Natl Acad Sci U S A. 86(2):476-80

 [14] Lee NL., Gielow WO., Wallace RG., 1981, Mechanism of araC autoregulation and the domains of two overlapping promoters, Pc and PBAD, in the L-arabinose regulatory region of Escherichia coli., Proc Natl Acad Sci U S A. 78(2):752-6

 [15] Lobell RB., Schleif RF., 1991, AraC-DNA looping: orientation and distance-dependent loop breaking by the cyclic AMP receptor protein., J Mol Biol. 218(1):45-54

 [16] Niland P., Huhne R., Muller-Hill B., 1996, How AraC interacts specifically with its target DNAs., J Mol Biol. 264(4):667-74

 [17] Reeder T., Schleif R., 1993, AraC protein can activate transcription from only one position and when pointed in only one direction., J Mol Biol. 231(2):205-18

 [18] Stoner C., Schleif R., 1983, The araE low affinity L-arabinose transport promoter. Cloning, sequence, transcription start site and DNA binding sites of regulatory proteins., J Mol Biol. 171(4):369-81

 [19] Hendrickson W., Stoner C., Schleif R., 1990, Characterization of the Escherichia coli araFGH and araJ promoters., J Mol Biol. 215(4):497-510

 [20] Lu Y., Flaherty C., Hendrickson W., 1992, AraC protein contacts asymmetric sites in the Escherichia coli araFGH promoter., J Biol Chem. 267(34):24848-57

 [21] Johnson CM., Schleif RF., 2000, Cooperative action of the catabolite activator protein and AraC in vitro at the araFGH promoter., J Bacteriol. 182(7):1995-2000

 [22] Reeder T., Schleif R., 1991, Mapping, sequence, and apparent lack of function of araJ, a gene of the Escherichia coli arabinose regulon., J Bacteriol. 173(24):7765-71

 [23] Desai TA., Rao CV., 2009, Regulation of arabinose and xylose metabolism in Escherichia coli., Appl Environ Microbiol

 [24] Stringer AM., Currenti S., Bonocora RP., Baranowski C., Petrone BL., Palumbo MJ., Reilly AA., Zhang Z., Erill I., Wade JT., 2014, Genome-scale analyses of Escherichia coli and Salmonella enterica AraC reveal noncanonical targets and an expanded core regulon., J Bacteriol. 196(3):660-71

 [25] Hendrickson W., Flaherty C., Molz L., 1992, Sequence elements in the Escherichia coli araFGH promoter., J Bacteriol. 174(21):6862-71

 [26] Miyada CG., Stoltzfus L., Wilcox G., 1984, Regulation of the araC gene of Escherichia coli: catabolite repression, autoregulation, and effect on araBAD expression., Proc Natl Acad Sci U S A. 81(13):4120-4

 [27] Lobell RB., Schleif RF., 1990, DNA looping and unlooping by AraC protein., Science. 250(4980):528-32

 [28] Hamilton EP., Lee N., 1988, Three binding sites for AraC protein are required for autoregulation of araC in Escherichia coli., Proc Natl Acad Sci U S A. 85(6):1749-53

 [29] Martin K., Huo L., Schleif RF., 1986, The DNA loop model for ara repression: AraC protein occupies the proposed loop sites in vivo and repression-negative mutations lie in these same sites., Proc Natl Acad Sci U S A. 83(11):3654-8

 [30] Carra JH., Schleif RF., 1993, Variation of half-site organization and DNA looping by AraC protein., EMBO J. 12(1):35-44

 [31] Gallegos MT., Michan C., Ramos JL., 1993, The XylS/AraC family of regulators., Nucleic Acids Res. 21(4):807-10

 [32] Soisson SM., MacDougall-Shackleton B., Schleif R., Wolberger C., 1997, The 1.6 A crystal structure of the AraC sugar-binding and dimerization domain complexed with D-fucose., J Mol Biol. 273(1):226-37

 [33] Rodgers ME., Holder ND., Dirla S., Schleif R., 2009, Functional modes of the regulatory arm of AraC., Proteins. 74(1):81-91

 [34] Frato KE., Schleif RF., 2009, A DNA-assisted binding assay for weak protein-protein interactions., J Mol Biol. 394(5):805-14

 [35] Seedorff J., Schleif R., 2011, Active role of the interdomain linker of AraC., J Bacteriol. 193(20):5737-46

 [36] Damjanovic A., Miller BT., Schleif R., 2013, Understanding the basis of a class of paradoxical mutations in AraC through simulations., Proteins. 81(3):490-8

 [37] Madar D., Dekel E., Bren A., Alon U., 2011, Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli., BMC Syst Biol. 5(1):111


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