RegulonDB RegulonDB 10.10: Operon Form
   

melR operon and associated TUs in Escherichia coli K-12 genome




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


Transcription unit          
Name: melR
Synonym(s): OP00050
Gene(s): melR   Genome Browser M3D Gene expression COLOMBOS
Note(s): MelR binds to five target sites, sites R (+2.5), 1' (-116.5), 1 (-136.5), 2 (-174.5), and 2' (-194.5), in the melR promoter, where the less-conserved site 2' (7 of 18 bases) binds MelR most weakly Belyaeva TA,2000 MelR binding to site 2' (-194.5) occurs only in the presence of melibiose Howard VJ,2002
Based on in vivo and in vitro methods, a repression model was proposed in which four DNA-bound MelR molecules are required for optimal autorepression of the melR operon [site 2 (-174.5), site 1 (-136.5), site 1' (-116.5, and site R (+2.5)] in the absence of melibiose. This means that MelR autoregulates its own expression by binding to site +2.5 and repressing its own promoter. This repression is reinforced by upstream binding of MelR Samarasinghe S,2008. Elrobh et al. (2013) showed that efficient repression of the melR promoter by MelR requires an interaction between the proximal R (+2.5) and distal 2 (-174.5) sites and results in loop formation, as seen with another AraC member (AraC controlling the araC-araBAD intergenic regulatory region) Elrobh MS, Webster CL, Samarasinghe S, Durose D, Busby SJ,2013
In the absence of melibiose, MelR is unable to activate the melAB promoter but autoregulates its own expression by repressing the melR promoter Wade JT,2000 Melibiose triggers MelR-dependent activation of the melAB promoter and relieves MelR-dependent repression of the melR promoter Howard VJ,2002. Wade JT,2000. Tamai E,2000. Caswell R, Webster C, Busby S,1992. Belyaeva TA,2000
Evidence: [BTEI] Boundaries of transcription experimentally identified
Reference(s): [1] Bourgerie SJ., et al., 1997
[2] Caswell R., et al., 1992
[3] Michan CM., et al., 1995
Promoter
Name: melRp
+1: 4341650
Sigma Factor: Sigma70 Sigmulon
Distance from start of the gene: 22
Sequence: agggtgaaaaccgtgctcccactcgcagtcatcctccctcactcctgccataattctgatAttccaggaaagagagccatc
                      -35                        -10        +1                   
Evidence: [ICWHO]
[TIM]
Reference(s): [4] Huerta AM., et al., 2003
[5] Wade JT., et al., 2000
[6] Webster C., et al., 1987
TF binding sites (TFBSs)
[CRP,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal CRP-cyclic-AMP activator melRp 4341681 4341702 -41.5 agagggtgaaAACCGTGCTCCCACTCGCAGTCatcctccctc nd [GEA], [AIBSCS], [APIORCISFBSCS], [BPP] [5], [7], [8], [10], [12]
remote CRP-cyclic-AMP activator melRp 4341795 4341816 -155.5 taaactcagaTCCTGCGTGAAGCAGCAGTAAAtctgagttta nd [GEA], [AIBSCS], [APIORCISFBSCS], [BPP] [5], [7], [8], [10]
[MelR,+] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
remote MelR-melibiose activator melRp 4341836 4341853 -194.5 tgcagaaaacCTCCGGCTTCCAGGTTGAgcattcccat nd [GEA], [BPP], [SM] [5]
[MelR,-] Phrase
Type Transcription factor Function Promoter Binding Sites Growth Conditions Evidence (Confirmed, Strong, Weak) Reference(s)
LeftPos RightPos Central Rel-Pos Sequence
proximal MelR repressor melRp 4341640 4341657 2.5 cctgccataaTTCTGATATTCCAGGAAAgagagccatc nd [GEA], [APIORCISFBSCS], [BPP], [SM] [7], [8], [9]
remote MelR-melibiose repressor melRp 4341758 4341775 -116.5 atgggaataaATTACCTGAAAAGCAGAGttttcggcct nd [GEA], [APIORCISFBSCS], [BPP] [5], [7], [9], [11]
remote MelR-melibiose repressor melRp 4341778 4341795 -136.5 gcagcagtaaATCTGAGTTTATGGGAATaaattacctg nd [GEA], [APIORCISFBSCS], [BPP] [5], [7], [9], [11]
remote MelR repressor melRp 4341816 4341833 -174.5 caggttgagcATTCCCATAAACTCAGATcctgcgtgaa nd [GEA], [BPP] [5], [7], [8], [9]


Evidence    

 [ICWHO] Inferred computationally without human oversight

 [TIM] Transcription initiation mapping

 [GEA] Gene expression analysis

 [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.

 [BPP] Binding of purified proteins

 [SM] Site mutation


Reference(s)    

 [1] Bourgerie SJ., Michan CM., Thomas MS., Busby SJ., Hyde EI., 1997, DNA binding and DNA bending by the MelR transcription activator protein from Escherichia coli., Nucleic Acids Res 25(9):1685-93

 [2] Caswell R., Williams J., Lyddiatt A., Busby S., 1992, Overexpression, purification and characterization of the Escherichia coli MelR transcription activator protein., Biochem J 287 ( Pt 2):493-9

 [3] Michan CM., Busby SJ., Hyde EI., 1995, The Escherichia coli MelR transcription activator: production of a stable fragment containing the DNA-binding domain., Nucleic Acids Res 23(9):1518-23

 [4] Huerta AM., Collado-Vides J., 2003, Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals., J Mol Biol 333(2):261-78

 [5] Wade JT., Belyaeva TA., Hyde EI., Busby SJ., 2000, Repression of the Escherichia coli melR promoter by MelR: evidence that efficient repression requires the formation of a repression loop., Mol Microbiol 36(1):223-9

 [6] Webster C., Kempsell K., Booth I., Busby S., 1987, Organisation of the regulatory region of the Escherichia coli melibiose operon., Gene 59(2-3):253-63

 [7] Belyaeva TA., Wade JT., Webster CL., Howard VJ., Thomas MS., Hyde EI., Busby SJ., 2000, Transcription activation at the Escherichia coli melAB promoter: the role of MelR and the cyclic AMP receptor protein., Mol Microbiol 36(1):211-22

 [8] Kahramanoglou C., Webster CL., El-Robh MS., Belyaeva TA., Busby SJ., 2006, Mutational analysis of the Escherichia coli melR gene suggests a two-state concerted model to explain transcriptional activation and repression in the melibiose operon., J Bacteriol 188(9):3199-207

 [9] Samarasinghe S., El-Robh MS., Grainger DC., Zhang W., Soultanas P., Busby SJ., 2008, Autoregulation of the Escherichia coli melR promoter: repression involves four molecules of MelR., Nucleic Acids Res 36(8):2667-76

 [10] Wade JT., Belyaeva TA., Hyde EI., Busby SJ., 2001, A simple mechanism for co-dependence on two activators at an Escherichia coli promoter., EMBO J 20(24):7160-7

 [11] Howard VJ., Belyaeva TA., Busby SJ., Hyde EI., 2002, DNA binding of the transcription activator protein MelR from Escherichia coli and its C-terminal domain., Nucleic Acids Res 30(12):2692-700

 [12] Zheng D., Constantinidou C., Hobman JL., Minchin SD., 2004, Identification of the CRP regulon using in vitro and in vivo transcriptional profiling., Nucleic Acids Res 32(19):5874-93

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