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FabR DNA-binding transcriptional repressor

Synonyms: FabR
Summary:
FabR, "Fatty acid biosynthesis Regulator," represses expression of the fabA and fabB genes, which are essential for the synthesis of monounsaturated fatty acids [3, 4] FabR directly influences membrane lipid homeostasis [3, 4, 5] It is a unique example of a transcription factor exclusively regulating expression of type II fatty acid synthase enzymes [3] The FabR consensus sequence has been identified as a palindromic sequence with a length of 18 bp [2, 3] DNA binding and repression require the binding of unsaturated acyl-ACP (acyl-acyl carrier protein) or acyl-CoA. Saturated acyl-ACP or acyl-CoA competes with the unsaturated fatty acids for binding to FabR but does not trigger DNA binding [6] Thus, FabR senses the ratio, rather than the absolute amount, of unsaturated and saturated fatty acids and adjusts expression of fabA and fabB to balance the composition of saturated and unsaturated acyl-ACP [6] L-threonine production increases when the fadR, fabR, and iclR regulators are deleted, suggesting that coupling fatty acid degradation and the L-threonine biosynthesis pathway via the glyoxylate shunt could efficiently increase L-threonine production [7] The binding site for FabR overlaps with the binding site for FadR, the transcriptional activator for fabA and fabB in the promoter regions of both fabA and fabB.
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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
FabR Functional   nd nd nd
Evolutionary Family: TetR/AcrR
TFBs length: 18
TFBs symmetry: inverted-repeat
Connectivity class: Local Regulator
Gene name: fabR
  Genome position: 4161067-4161771
  Length: 705 bp / 234 aa
Operon name: fabR-yijD
TU(s) encoding the TF:
Transcription unit        Promoter
fabR-yijD
 


Regulon       
Regulated gene(s) fabA, fabB
Multifun term(s) of regulated gene(s)
fatty acids and phosphatidic acid (2)
Regulated operon(s) fabA, fabB
First gene in the operon(s) fabA, fabB
Simple and complex regulons FabR,FadR
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[FabR,-](2)


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
  FabR repressor fabAp Sigma70 -19.5 -47.5 fabA
ggacttgttcAGCGTACACGTGTTAGCTatcctgcgtg
 1016509 1016526 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-AINF-SIMILAR-TO-CONSENSUS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [2], [3]
  FabR repressor fabBp Sigma70 -20.5 -56.5 fabB
ggacttgttcGGCGTACAAGTGTACGCTattgtgcatt
 2441653 2441670 [EXP-IEP-GENE-EXPRESSION-ANALYSIS], [COMP-HINF-SIMILAR-TO-CONSENSUS], [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS], [EXP-IDA-BINDING-OF-PURIFIED-PROTEINS] C [1], [1], [2], [3]


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
Promoter-target gene evolutionary conservation


Evidence    

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

 [COMP-AINF-SIMILAR-TO-CONSENSUS] Automated inference based on similarity to consensus sequences

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

 [EXP-IDA-BINDING-OF-CELLULAR-EXTRACTS] Binding of cellular extracts

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


Reference(s)    

 [1] Feng Y., Cronan JE., 2011, Complex binding of the FabR repressor of bacterial unsaturated fatty acid biosynthesis to its cognate promoters., Mol Microbiol 80(1):195-218

 [2] McCue L., Thompson W., Carmack C., Ryan MP., Liu JS., Derbyshire V., Lawrence CE., 2001, Phylogenetic footprinting of transcription factor binding sites in proteobacterial genomes., Nucleic Acids Res 29(3):774-82

 [3] Zhang YM., Marrakchi H., Rock CO., 2002, The FabR (YijC) transcription factor regulates unsaturated fatty acid biosynthesis in Escherichia coli., J Biol Chem 277(18):15558-65

 [4] Marrakchi H, Zhang YM, Rock CO, 2002, Mechanistic diversity and regulation of Type II fatty acid synthesis., Biochem Soc Trans, 30(Pt 6):1050 10.1042/bst0301050

 [5] Cronan JE, Gelmann EP, 1975, Physical properties of membrane lipids: biological relevance and regulation., Bacteriol Rev, 39(3):232 10.1128/br.39.3.232-256.1975

 [6] Zhu K, Zhang YM, Rock CO, 2009, Transcriptional regulation of membrane lipid homeostasis in Escherichia coli., J Biol Chem, 284(50):34880 10.1074/jbc.M109.068239

 [7] Yang J, Fang Y, Wang J, Wang C, Zhao L, Wang X, 2019, Deletion of regulator-encoding genes fadR, fabR and iclR to increase L-threonine production in Escherichia coli., Appl Microbiol Biotechnol, 103(11):4549 10.1007/s00253-019-09818-8

 [8] Ramos JL, Martínez-Bueno M, Molina-Henares AJ, Terán W, Watanabe K, Zhang X, Gallegos MT, Brennan R, Tobes R, 2005, The TetR family of transcriptional repressors., Microbiol Mol Biol Rev, 69(2):326 10.1128/MMBR.69.2.326-356.2005

 [9] Bateman A., Birney E., Durbin R., Eddy SR., Howe KL., Sonnhammer EL., 2000, The Pfam protein families database., Nucleic Acids Res 28(1):263-6

 [10] Perez-Rueda E., Collado-Vides J., 2000, The repertoire of DNA-binding transcriptional regulators in Escherichia coli K-12., Nucleic Acids Res 28(8):1838-47

 [11] Shao X, Zhang W, Umar MI, Wong HY, Seng Z, Xie Y, Zhang Y, Yang L, Kwok CK, Deng X, 2020, RNA G-Quadruplex Structures Mediate Gene Regulation in Bacteria., mBio, 11(1):None 10.1128/mBio.02926-19

 [12] Zhang YM, Rock CO, 2009, Transcriptional regulation in bacterial membrane lipid synthesis., J Lipid Res, 50 Suppl(None):S115 10.1194/jlr.R800046-JLR200

 [13] Fujita Y, Matsuoka H, Hirooka K, 2007, Regulation of fatty acid metabolism in bacteria., Mol Microbiol, 66(4):829 10.1111/j.1365-2958.2007.05947.x


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