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MetR DNA-binding transcriptional dual regulator

Synonyms: MetR, MetR-L-homocysteine
Summary:
MetR participates in controlling several genes involved in methionine biosynthesis [2]and a gene involved in protection against nitric oxide [7] Homocysteine, an intermediate in the biosynthesis of methionine [14] binds to MetR and enhances the activity of some MetR-activated promoters (i.e., metE and glyA) by enhancing the affinity in DNA-binding sites [2, 4] But homocysteine is also able to decrease the activity of other promoters that are activated (i.e., metH, metA, and hmp) or repressed (i.e., metR) by MetR [2, 10, 14] The glyA and hmp genes are transcribed divergently and have a common regulatory region that contains two MetR DNA-binding sites. When homocysteine is present, MetR binds to two MetR sites and activates glyA and represses hmp transcription, but in the absence of homocysteine MetR binds only one site and activates hmp and represses glyA transcription [7] MetR appears to first bind DNA and then homocysteine causes the effect on transcription [10] The nitrosated compound S-nitrosoglutathione (GSNO) removes homocysteine by nitrosation [7] The RNA polymerase and MetR interact for transcription activation, but distinct residues of RNA polymerase are involved in different promoters because the MetR-binding sites are located at different positions [4, 15].
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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
MetR Functional   Apo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP-SITE-MUTATION] S [1], [2]
MetR-L-homocysteine Functional Allosteric Holo [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP-SITE-MUTATION] S [1], [2]
Evolutionary Family: LysR
TFBs length: 15
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: metR
  Genome position: 4011863-4012816
  Length: 954 bp / 317 aa
Operon name: metR
TU(s) encoding the TF:
Transcription unit        Promoter
metR
metRp1
metR
metRp2


Regulon       
Regulated gene(s) glyA, hmp, metE, metH, metR
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
methionine (3)
amino acids (1)
glycine (1)
formyl-THF biosynthesis (1)
unassigned reversible reactions (1)
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Regulated operon(s) glyA, hmp, metE, metH, metR
First gene in the operon(s) glyA, hmp, metE, metH, metR
Simple and complex regulons FNR,Fur,MetR,NsrR,ppGpp
Fur,MetR
MetJ,MetR
MetJ,MetR,OxyR
MetR,PurR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MetR,+](4)
[MetR,-](3)


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
  MetR-L-homocysteine activator glyAp Sigma70 -143.0 -210.0 glyA
atgtgatgaaGTGAAAAATTTGCATcacaaacctg
 2685710 2685724 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [3], [3], [4], [4], [5], [6], [6], [7], [7], [8]
  MetR-L-homocysteine repressor glyAp Sigma70 -143.0 -210.0 glyA
atgtgatgaaGTGAAAAATTTGCATcacaaacctg
 2685710 2685724 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [3], [3], [4], [4], [5], [6], [6], [7], [7], [8]
  MetR-L-homocysteine activator glyAp Sigma70 -121.0 -188.0 glyA
catcacaaacCTGAAAAGAAATCCGtttccggttg
 2685688 2685702 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [3], [3], [4], [4], [5], [5], [6], [6], [8]
  MetR activator hmpp Sigma38 -80.0 -118.0 hmp
caggtttgtgATGCAAATTTTTCACttcatcacat
 2685710 2685724 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-IMP], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IMP-SITE-MUTATION] C [3], [3], [4], [5], [6], [7], [7], [8]
  MetR-L-homocysteine activator metEp nd -62.0 -231.0 metE
tacttcgatcATGAAAGTCCTTCACttcggcatga
 4012815 4012829 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [8], [9], [9], [10], [11], [11], [12]
  MetR-L-homocysteine activator metEp nd -41.0 -210.0 metE
tcacttcggcATGAATAATTTGCGCttgaggaata
 4012836 4012850 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [8], [9], [9], [10], [11], [12]
  MetR activator metHp1 Sigma70 -57.0 -102.0 metH
tgagttaatgTTGAACAAATCTCATgttgcgtggt
 4223719 4223733 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS] W [9], [10], [11], [13], [13]
  MetR-L-homocysteine repressor metRp1 nd 13.0 -27.0 metR
tattcctcaaGCGCAAATTATTCATgccgaagtga
 4012836 4012850 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [8], [9], [9], [10], [11], [12]
  MetR-L-homocysteine repressor metRp1 nd 34.0 -6.0 metR
tcatgccgaaGTGAAGGACTTTCATgatcgaagta
 4012815 4012829 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [8], [9], [9], [10], [11], [11], [12]
  MetR-L-homocysteine repressor metRp2 nd -6.0 -27.0 metR
tattcctcaaGCGCAAATTATTCATgccgaagtga
 4012836 4012850 [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS], [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] S [8], [9], [9], [10], [11], [12]
  MetR-L-homocysteine repressor metRp2 nd 16.0 -6.0 metR
tcatgccgaaGTGAAGGACTTTCATgatcgaagta
 4012815 4012829 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-DAP-SEQ], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [2], [8], [9], [9], [10], [11], [11], [12]


Alignment and PSSM for MetR TFBSs    

Aligned TFBS of MetR   
  Sequence
  GATGCAAATTTTTCACTT
  CATGAAAGTCCTTCACTT
  CATGAATAATTTGCGCTT
  CCTGAAAAGAAATCCGTT
  GTTGAACAAATCTCATGT

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

Consensus    
;	consensus.strict             	caTGaAaaaatttCactT
;	consensus.strict.rc          	AAGTGAAATTTTTTCATG
;	consensus.IUPAC              	saTGaAaawwtttCactT
;	consensus.IUPAC.rc           	AAGTGAAAWWTTTTCATS
;	consensus.regexp             	[cg]aTGaAaa[at][at]tttCactT
;	consensus.regexp.rc          	AAGTGAAA[AT][AT]TTTTCAT[CG]

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

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

 [EXP-IMP-SITE-MUTATION] Site mutation

 [EXP-IMP] Inferred from mutant phenotype

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

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


Reference(s)    

 [1] Maxon ME., Wigboldus J., Brot N., Weissbach H., 1990, Structure-function studies on Escherichia coli MetR protein, a putative prokaryotic leucine zipper protein., Proc Natl Acad Sci U S A 87(18):7076-9

 [2] Weissbach H., Brot N., 1991, Regulation of methionine synthesis in Escherichia coli., Mol Microbiol 5(7):1593-7

 [3] Lorenz E., Stauffer GV., 1995, Characterization of the MetR binding sites for the glyA gene of Escherichia coli., J Bacteriol 177(14):4113-20

 [4] Lorenz E., Stauffer GV., 1996, RNA polymerase, PurR and MetR interactions at the glyA promoter of Escherichia coli., Microbiology 142 ( Pt 7):1819-24

 [5] Lorenz E., Stauffer GV., 1996, MetR-mediated repression of the glyA gene in Escherichia coli., FEMS Microbiol Lett 144(2-3):229-33

 [6] Lorenz E., Stauffer GV., 1996, Cooperative MetR binding in the Escherichia coli glyA control region., FEMS Microbiol Lett 137(2-3):147-52

 [7] Membrillo-Hernandez J., Coopamah MD., Channa A., Hughes MN., Poole RK., 1998, A novel mechanism for upregulation of the Escherichia coli K-12 hmp (flavohaemoglobin) gene by the 'NO releaser', S-nitrosoglutathione: nitrosation of homocysteine and modulation of MetR binding to the glyA-hmp intergenic region., Mol Microbiol 29(4):1101-12

 [8] 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

 [9] Cai XY., Maxon ME., Redfield B., Glass R., Brot N., Weissbach H., 1989, Methionine synthesis in Escherichia coli: effect of the MetR protein on metE and metH expression., Proc Natl Acad Sci U S A 86(12):4407-11

 [10] Cai XY., Redfield B., Maxon M., Weissbach H., Brot N., 1989, The effect of homocysteine on MetR regulation of metE, metR and metH expression in vitro., Biochem Biophys Res Commun 163(1):79-83

 [11] Jafri S., Urbanowski ML., Stauffer GV., 1995, A mutation in the rpoA gene encoding the alpha subunit of RNA polymerase that affects metE-metR transcription in Escherichia coli., J Bacteriol 177(3):524-9

 [12] Maxon ME., Redfield B., Cai XY., Shoeman R., Fujita K., Fisher W., Stauffer G., Weissbach H., Brot N., 1989, Regulation of methionine synthesis in Escherichia coli: effect of the MetR protein on the expression of the metE and metR genes., Proc Natl Acad Sci U S A 86(1):85-9

 [13] Old IG., Margarita D., Glass RE., Saint Girons I., 1990, Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2., Gene 87(1):15-21

 [14] Urbanowski ML., Stauffer GV., 1989, Role of homocysteine in metR-mediated activation of the metE and metH genes in Salmonella typhimurium and Escherichia coli., J Bacteriol 171(6):3277-81

 [15] Fritsch PS, Urbanowski ML, Stauffer GV, 2000, Role of the RNA polymerase alpha subunits in MetR-dependent activation of metE and metH: important residues in the C-terminal domain and orientation requirements within RNA polymerase., J Bacteriol, 182(19):5539 10.1128/JB.182.19.5539-5550.2000

 [16] Schell MA., 1993, Molecular biology of the LysR family of transcriptional regulators., Annu Rev Microbiol 47:597-626


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