Genomes and Genes
Gene Symbol: lacI
Description: lactose-inducible lac operon transcriptional repressor
Alias: ECK0342, JW0336
Species: Escherichia coli str. K-12 substr. MG1655
- Lewis M. The lac repressor. C R Biol. 2005;328:521-48 pubmed..The structures of lac repressor, bound to its operator and inducer, have also been invaluable for interpreting a plethora of biochemical and genetic data. ..
- Saiz L, Rubi J, Vilar J. Inferring the in vivo looping properties of DNA. Proc Natl Acad Sci U S A. 2005;102:17642-5 pubmed..These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought. ..
- Zhang Y, McEwen A, Crothers D, Levene S. Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA looping. PLoS ONE. 2006;1:e136 pubmed
- van Hoek M, Hogeweg P. In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose. Biophys J. 2006;91:2833-43 pubmed..Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers. ..
- Müller Hill B, Crapo L, Gilbert W. Mutants that make more lac repressor. Proc Natl Acad Sci U S A. 1968;59:1259-64 pubmed
- Kalodimos C, Bonvin A, Salinas R, Wechselberger R, Boelens R, Kaptein R. Plasticity in protein-DNA recognition: lac repressor interacts with its natural operator 01 through alternative conformations of its DNA-binding domain. EMBO J. 2002;21:2866-76 pubmed
- Perros M, Steitz T. DNA looping and lac repressor-CAP interaction. Science. 1996;274:1929-30; author reply 1931-2 pubmed
- Guido N, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor C, et al. A bottom-up approach to gene regulation. Nature. 2006;439:856-60 pubmed..This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation. ..
- Kopke Salinas R, Folkers G, Bonvin A, Das D, Boelens R, Kaptein R. Altered specificity in DNA binding by the lac repressor: a mutant lac headpiece that mimics the gal repressor. Chembiochem. 2005;6:1628-37 pubmed
- Vilar J, Guet C, Leibler S. Modeling network dynamics: the lac operon, a case study. J Cell Biol. 2003;161:471-6 pubmed..We integrate three different levels of description (molecular, cellular, and that of cell population) into a single model, which seems to capture many experimental aspects of the system. ..
- Santillan M. Bistable behavior in a model of the lac operon in Escherichia coli with variable growth rate. Biophys J. 2008;94:2065-81 pubmed..The results are discussed in regard to the bistable behavior of the lactose operon. Special attention is paid to the effect that a variable growth rate has on the system dynamics. ..
- Müller Hill B. The function of auxiliary operators. Mol Microbiol. 1998;29:13-8 pubmed..For this purpose, a strategy is used over and over again. It is called increase in local concentration. How Escherichia coli uses this strategy efficiently is discussed. ..
- Yildirim N, Mackey M. Feedback regulation in the lactose operon: a mathematical modeling study and comparison with experimental data. Biophys J. 2003;84:2841-51 pubmed
- Swigon D, Coleman B, Olson W. Modeling the Lac repressor-operator assembly: the influence of DNA looping on Lac repressor conformation. Proc Natl Acad Sci U S A. 2006;103:9879-84 pubmed
- van Hoek M, Hogeweg P. The effect of stochasticity on the lac operon: an evolutionary perspective. PLoS Comput Biol. 2007;3:e111 pubmed..Moreover, we demonstrate that in silico evolution in a quantitative model, by mutating the parameters of interest, is a promising way to unravel the functional properties of biological systems. ..
- Abo T, Inada T, Ogawa K, Aiba H. SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon. EMBO J. 2000;19:3762-9 pubmed..COLI: cells. More specifically, we report that the lacI mRNA encoding Lac repressor (LacI) is a specific natural target for trans-translation...
- Lewis M, Chang G, Horton N, Kercher M, Pace H, Schumacher M, et al. Crystal structure of the lactose operon repressor and its complexes with DNA and inducer. Science. 1996;271:1247-54 pubmed..Its key component is the lac repressor, a product of the lacI gene...
- Sartorius J, Lehming N, Kisters B, von Wilcken Bergmann B, Müller Hill B. lac repressor mutants with double or triple exchanges in the recognition helix bind specifically to lac operator variants with multiple exchanges. EMBO J. 1989;8:1265-70 pubmed..Mutations of residues 1 and 2 may be combined with a mutation of residue 6. The resulting mutant protein binds specifically to an operator variant with three symmetric exchanges in base pairs 4, 5 and 6. ..
- Ozbudak E, Thattai M, Lim H, Shraiman B, van Oudenaarden A. Multistability in the lactose utilization network of Escherichia coli. Nature. 2004;427:737-40 pubmed..The phase diagram thus serves as a sensitive probe of molecular interactions and as a powerful tool for rational network design. ..
- Vossen K, Stickle D, Fried M. The mechanism of CAP-lac repressor binding cooperativity at the E. coli lactose promoter. J Mol Biol. 1996;255:44-54 pubmed..reduced by the removal of DNA located upstream of the CAP binding site or by substitution of the dimeric lacI-18 mutant repressor for the wild-type tetrameric protein...
- ..Ultimately, these novel repressors could be evolved to recognize eukaryotic promoters and used to regulate gene expression in mammalian systems. ..
- Müller Hill B. What is life? The paradigm of DNA and protein cooperation at high local concentrations. Mol Microbiol. 2006;60:253-5 pubmed..The examples of Lac and Lambda repressors of Escherichia coli are presented and discussed here as useful paradigms of mechanisms for achieving high local concentrations of interacting protein protomers. ..
- Camas F, Alm E, Poyatos J. Local gene regulation details a recognition code within the LacI transcriptional factor family. PLoS Comput Biol. 2010;6:e1000989 pubmed publisher..Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs)...
- Burstein C. [Role of transgalactosidations in induction of the lactose operon in Escherichia coli]. Bull Soc Chim Biol (Paris). 1965;47:1901-4 pubmed
- Rolseth S, Fried V, Hall B. A mutant Ebg enzyme that converts lactose into an inducer of the lac operon. J Bacteriol. 1980;142:1036-9 pubmed..We report here the isolation of a mutant Ebg beta-galactosidase which is capable of converting lactose into an inducer of the lac operon. ..
- Lehming N, Sartorius J, Kisters Woike B, von Wilcken Bergmann B, Müller Hill B. Mutant lac repressors with new specificities hint at rules for protein--DNA recognition. EMBO J. 1990;9:615-21 pubmed..Rules of recognition can be derived for 16 symmetric operators. They also apply to the gal repressor and possibly to other bacterial repressors. ..
- Lehming N, Sartorius J, Niemöller M, Genenger G, v Wilcken Bergmann B, Müller Hill B. The interaction of the recognition helix of lac repressor with lac operator. EMBO J. 1987;6:3145-53 pubmed..The other plasmid carries the gene coding for the repressor, in our case a semisynthetic lacI gene of which parts can be exchanged in a cassette-like manner...
- Hammar P, Leroy P, Mahmutovic A, Marklund E, Berg O, Elf J. The lac repressor displays facilitated diffusion in living cells. Science. 2012;336:1595-8 pubmed publisher..Furthermore, the repressor frequently (>90%) slides over its natural lacO(1) operator several times before binding. This suggests a trade-off between rapid search on nonspecific sequences and fast binding at the specific sequence...
- Hastings P, Slack A, Petrosino J, Rosenberg S. Adaptive amplification and point mutation are independent mechanisms: evidence for various stress-inducible mutation mechanisms. PLoS Biol. 2004;2:e399 pubmed..We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression. ..
- Tang M, Wang S, Wang T, Zhao S, Wu Y, Wu L, et al. Mutational spectrum of the lacI gene in Escherichia coli K12 induced by low-energy ion beam. Mutat Res. 2006;602:163-9 pubmedThe mutational spectrum of the genomic lacI gene induced by low-energy nitrogen ion irradiation in wild type Escherichia coli strain W3110 were compared with the spontaneous and the vacuum controls...
- Cunha S, Woldringh C, Odijk T. Restricted diffusion of DNA segments within the isolated Escherichia coli nucleoid. J Struct Biol. 2005;150:226-32 pubmed..Restriction of a DNA sequence to a small region of the nucleoid is tentatively related to the existence of so-called supercoiling domains. ..
- Kuhlman T, Zhang Z, Saier M, Hwa T. Combinatorial transcriptional control of the lactose operon of Escherichia coli. Proc Natl Acad Sci U S A. 2007;104:6043-8 pubmed..Specifically, our analysis indicates that the sensitivity of the inducer response results from LacR-mediated DNA looping, which is significantly enhanced by CRP. ..
- Williams B, Paigen K. Relationships between the regulation of the lactose and galactose operons of Escherichia coli. J Bacteriol. 1969;97:769-75 pubmed..For this operon, the differential rate of enzyme synthesis is set by the relative intracellular concentrations of inducer (fucose) and repressor (isopropylthiogalactoside). ..
- Swint Kruse L, Matthews K. Allostery in the LacI/GalR family: variations on a theme. Curr Opin Microbiol. 2009;12:129-37 pubmed publisherThe lactose repressor protein (LacI) was among the very first genetic regulatory proteins discovered, and more than 1000 members of the bacterial LacI/GalR family are now identified...
- Slijper M, Boelens R, Davis A, Konings R, van der Marel G, van Boom J, et al. Backbone and side chain dynamics of lac repressor headpiece (1-56) and its complex with DNA. Biochemistry. 1997;36:249-54 pubmed..These results suggest that the mobility of the regions within lac HP56 important for complexation, i.e., the loop and the DNA-contacting side chains, is essential for a good fit onto the counterparts of the target DNA. ..
- Swint Kruse L, Larson C, Pettitt B, Matthews K. Fine-tuning function: correlation of hinge domain interactions with functional distinctions between LacI and PurR. Protein Sci. 2002;11:778-94 pubmedb>LacI and PurR are highly homologous proteins. Their functional units are homodimers, with an N-terminal DNA binding domain that comprises the helix-turn-helix (HTH), N-linker, and hinge regions from both monomers...
- Leive L, Kollin V. Synthesis, utilization and degradation of lactose operon mRNA in Escherichia coli. J Mol Biol. 1967;24:247-59 pubmed
- Epstein W, Naono S, Gros F. Synthesis of enzymes of the lactose operon during diauxic growth of Escherichia coli. Biochem Biophys Res Commun. 1966;24:588-92 pubmed
- Becker N, Kahn J, Maher L. Effects of nucleoid proteins on DNA repression loop formation in Escherichia coli. Nucleic Acids Res. 2007;35:3988-4000 pubmed..These results suggest that host nucleoid proteins can directly facilitate or inhibit DNA looping in bacteria. ..
- Oehler S, Müller Hill B. High local concentration: a fundamental strategy of life. J Mol Biol. 2010;395:242-53 pubmed publisher..Local increase in concentration leads to cooperative or competitive interactions between molecules. It is an important principle of life. ..
- Kalisky T, Dekel E, Alon U. Cost-benefit theory and optimal design of gene regulation functions. Phys Biol. 2007;4:229-45 pubmed..The present cost-benefit theory can be used to understand the shape of other gene regulatory functions in terms of environment and noise constraints. ..
- Wilson C, Zhan H, Swint Kruse L, Matthews K. The lactose repressor system: paradigms for regulation, allosteric behavior and protein folding. Cell Mol Life Sci. 2007;64:3-16 pubmed..Thus, the lac system continues to advance our molecular understanding of genetic control and the relationship between sequence, structure and function. ..
- Roth J, Andersson D. Rebuttal: adaptive point mutation (Rosenberg and Hastings). J Bacteriol. 2004;186:4844 pubmed
- Beckwith J, Signer E. Transposition of the lac region of Escherichia coli. I. Inversion of the lac operon and transduction of lac by phi80. J Mol Biol. 1966;19:254-65 pubmed
- Swint Kruse L, Zhan H, Fairbanks B, Maheshwari A, Matthews K. Perturbation from a distance: mutations that alter LacI function through long-range effects. Biochemistry. 2003;42:14004-16 pubmedAllosteric modification of ligand binding is central to LacI transcription control. Recently, the conformational change between LacI operator- and inducer-bound states was simulated with targeted molecular dynamics (TMD) [Flynn, T. C...
- Horowitz H, Platt T. A termination site for LacI transcription is between the CAP site and the lac promoter. J Biol Chem. 1982;257:11740-6 pubmed
- Lehming N, Sartorius J, Oehler S, von Wilcken Bergmann B, Müller Hill B. Recognition helices of lac and lambda repressor are oriented in opposite directions and recognize similar DNA sequences. Proc Natl Acad Sci U S A. 1988;85:7947-51 pubmed..The consequences of this model are discussed in regard to various phage and bacterial repressor operator systems. ..
- von Hippel P. Biochemistry. Completing the view of transcriptional regulation. Science. 2004;305:350-2 pubmed
- Steege D. 5'-Terminal nucleotide sequence of Escherichia coli lactose repressor mRNA: features of translational initiation and reinitiation sites. Proc Natl Acad Sci U S A. 1977;74:4163-7 pubmed..Third, the formation of stable secondary structures predicted for the untranslated I mRNA beyond chain-terminating nonsense mutations may prevent ribosome access to some potential reinitiation sites. ..
- Gordon A, Burns P, Fix D, Yatagai F, Allen F, Horsfall M, et al. Missense mutation in the lacI gene of Escherichia coli. Inferences on the structure of the repressor protein. J Mol Biol. 1988;200:239-51 pubmed..We have been using the lacI gene-repressor protein system to study the mutational specificity of spontaneous and induced mutation...
- Gillard N, Goffinont S, Buré C, Davidkova M, Maurizot J, Cadene M, et al. Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor. Biochem J. 2007;403:463-72 pubmed..The loss of repressor function is thus correlated with chemical modifications and conformational changes of the headpiece. ..
- Rosenberg S, Hastings P. Adaptive point mutation and adaptive amplification pathways in the Escherichia coli Lac system: stress responses producing genetic change. J Bacteriol. 2004;186:4838-43 pubmed
- Bharatan S, Reddy M, Gowrishankar J. Distinct signatures for mutator sensitivity of lacZ reversions and for the spectrum of lacI/lacO forward mutations on the chromosome of nondividing Escherichia coli. Genetics. 2004;166:681-92 pubmed..Escherichia coli, first to eliminate all growth-associated chromosomal reversions in lacZ or forward mutations in lacI/lacO by incubation at the restrictive temperature and subsequently to recover (as papillae) spontaneous mutations ..
- Goffinont S, Davidkova M, Spotheim Maurizot M. Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor. Biochem Biophys Res Commun. 2009;386:300-4 pubmed publisher..The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain. ..
- Semsey S, Jauffred L, Csiszovszki Z, Erdossy J, St ger V, Hansen S, et al. The effect of LacI autoregulation on the performance of the lactose utilization system in Escherichia coli. Nucleic Acids Res. 2013;41:6381-90 pubmed publisher..Here we study the effect of autoregulation on intracellular LacI levels and also show that cAMP-CRP binding does not affect the efficiency of autoregulation...
- Müller Hill B, Kania J. Lac repressor can be fused to beta-galactosidase. Nature. 1974;249:561-3 pubmed
- Balaeff A, Mahadevan L, Schulten K. Structural basis for cooperative DNA binding by CAP and lac repressor. Structure. 2004;12:123-32 pubmed..Using the multiscale approach, we build an all-atom model of the ternary complex that suggests a series of further experimental investigations. ..
- Betz J. Cloning and characterization of several dominant-negative and tight-binding mutants of lac repressor. Gene. 1986;42:283-92 pubmedUsing both general recombination and molecular cloning techniques, 13I-, I-d and Itb missense mutations in the lacI gene were transferred from F'lacIq episomes to ColE1 derivative plasmids...
- Mazier S, Villette S, Goffinont S, Renouard S, Maurizot J, Genest D, et al. Radiation damage to a DNA-binding protein. Combined circular dichroism and molecular dynamics simulation analysis. Radiat Res. 2008;170:604-12 pubmed publisher..This conclusion should hold for all proteins containing radiosensitive amino acids in their DNA-binding site. ..
- Müller Hill B. Suppressible regulator constitutive mutants of the lactose system in Escherichia coli. J Mol Biol. 1966;15:374-6 pubmed
- Langridge J. Mutations conferring quantitative and qualitative increases in beta-galactosidase activity in Escherichia coli. Mol Gen Genet. 1969;105:74-83 pubmed
- Xu J, Matthews K. Flexibility in the inducer binding region is crucial for allostery in the Escherichia coli lactose repressor. Biochemistry. 2009;48:4988-98 pubmed publisherLactose repressor protein (LacI) utilizes an allosteric mechanism to regulate transcription in Escherichia coli, and the transition between inducer- and operator-bound states has been simulated by targeted molecular dynamics (TMD)...
- Blommel P, Becker K, Duvnjak P, Fox B. Enhanced bacterial protein expression during auto-induction obtained by alteration of lac repressor dosage and medium composition. Biotechnol Prog. 2007;23:585-98 pubmed..coli is based on diauxic growth resulting from dynamic function of lac operon regulatory elements (lacO and LacI) in mixtures of glucose, glycerol, and lactose...
- Narang A. Effect of DNA looping on the induction kinetics of the lac operon. J Theor Biol. 2007;247:695-712 pubmed..This suggests that repressor overexpression can induce bistability in systems, such as growth of E. coli on lactose, that are otherwise monostable. ..
- Shineberg B. Mutations partially inactivating the lactose repressor of Escherichia coli. J Bacteriol. 1974;119:500-7 pubmed..An explanation is proposed for the apparent sensitivity of this repressor function to partial inactivation as the result of amino acid substitutions. ..
- ..Understanding how effector molecules alter the thermodynamic properties of the repressor is essential for establishing a detailed understanding of gene regulation. ..
- Borukhov S, Lee J. RNA polymerase structure and function at lac operon. C R Biol. 2005;328:576-87 pubmed..by transcription activators, such as cyclic AMP-receptor protein, CRP, and negatively regulated by lac-repressor, LacI. In this review, we discuss the recent progress in structural and biochemical studies of RNAP and its binary and ..
- Kepes A. Sequential transcription and translation in the lactose operon of Escherichia coli. Biochim Biophys Acta. 1967;138:107-23 pubmed
- Bell C, Barry J, Matthews K, Lewis M. Structure of a variant of lac repressor with increased thermostability and decreased affinity for operator. J Mol Biol. 2001;313:99-109 pubmed
- Brickner J, Walter P. Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol. 2004;2:e342 pubmed..Gene recruitment to the nuclear periphery, therefore, is a dynamic process and appears to play an important regulatory role. ..
- Sartorius J, Lehming N, Kisters Woike B, von Wilcken Bergmann B, Müller Hill B. The roles of residues 5 and 9 of the recognition helix of Lac repressor in lac operator binding. J Mol Biol. 1991;218:313-21 pubmed..They further suggest that residue 9 of the recognition helix (asparagine 25) interacts non-specifically with a phosphate of the DNA backbone, possibly between base-pairs 2 and 3. ..
- Xu J, Liu S, Chen M, Ma J, Matthews K. Altering residues N125 and D149 impacts sugar effector binding and allosteric parameters in Escherichia coli lactose repressor. Biochemistry. 2011;50:9002-13 pubmed publisherLactose repressor protein (LacI), a negative transcriptional regulator in Escherichia coli, relies on an allosteric conformational change for its function...
- Zurla C, Samuely T, Bertoni G, Valle F, Dietler G, Finzi L, et al. Integration host factor alters LacI-induced DNA looping. Biophys Chem. 2007;128:245-52 pubmed..coli. In single molecule experiments, we show that both specific bending and non-specific compaction alter LacI-mediated looping of DNA...
- Tomshine J, Kaznessis Y. Optimization of a stochastically simulated gene network model via simulated annealing. Biophys J. 2006;91:3196-205 pubmed..The repressilator is optimized to give oscillations of an arbitrary specified period. These optimized designs may then provide a starting-point for the selection of genetic components needed to realize an in vivo system. ..
- Santillan M, Mackey M. Quantitative approaches to the study of bistability in the lac operon of Escherichia coli. J R Soc Interface. 2008;5 Suppl 1:S29-39 pubmed publisher..A review of the literature in which this bistable phenomenon has been studied from a mathematical modelling viewpoint is then given. We conclude with some brief remarks. ..
- Morgan M, Okamoto K, Kahn J, English D. Single-molecule spectroscopic determination of lac repressor-DNA loop conformation. Biophys J. 2005;89:2588-96 pubmedThe Escherichia coli lactose repressor protein (LacI) provides a classic model for understanding protein-induced DNA looping. LacI has a C-terminal four-helix bundle tetramerization domain that may act as a flexible hinge...
- Farabaugh P. Sequence of the lacI gene. Nature. 1978;274:765-9 pubmedThe structural gene for the lac repressor of Escherichia coli, the lacI gene has been sequenced. This 1,080 base pair region of the E. coli chromosome codes for the lac repressor protein of 360 amino acids...
- Görke B, Reinhardt J, Rak B. Activity of Lac repressor anchored to the Escherichia coli inner membrane. Nucleic Acids Res. 2005;33:2504-11 pubmed..Other mechanisms, like induction of a conformational change or masking of binding domains are required additionally. ..
- Spronk C, Bonvin A, Radha P, Melacini G, Boelens R, Kaptein R. The solution structure of Lac repressor headpiece 62 complexed to a symmetrical lac operator. Structure. 1999;7:1483-92 pubmed..In addition, the structural features of the hinge region provide detailed insight into the protein-protein and protein-DNA interactions responsible for the high affinity of the repressor for operator DNA. ..
- Choi P, Cai L, Frieda K, Xie X. A stochastic single-molecule event triggers phenotype switching of a bacterial cell. Science. 2008;322:442-6 pubmed publisher..Hence, a stochastic single-molecule event determines a cell's phenotype. ..
- Stenberg K, Vihinen M. Crystal structure of a 1.6-hexanediol bound tetrameric form of Escherichia coli lac-repressor refined to 2.1 A resolution. Proteins. 2009;75:748-59 pubmed publisherWe report the structure of a novel tetrameric form of the lactose repressor (LacI) protein from Escherichia coli refined to 2.1 A resolution. The tetramer is bound to 1...
- Yudkin M. Catabolite repression of the lac operon. The contribution f trascriptional repression. Biochem J. 1969;114:307-11 pubmed..It is also concluded that the extent of translational repression varies between strains. ..
- Smith T, Sadler J. The nature of lactose operator constitive mutations. J Mol Biol. 1971;59:273-305 pubmed
- Saier M, Straud H, Massman L, Judice J, Newman M, Feucht B. Permease-specific mutations in Salmonella typhimurium and Escherichia coli that release the glycerol, maltose, melibiose, and lactose transport systems from regulation by the phosphoenolpyruvate:sugar phosphotransferase system. J Bacteriol. 1978;133:1358-67 pubmed
- Miller J. Structure of a paradigm. Nat Struct Biol. 1996;3:310-2 pubmed
- Spronk C, Folkers G, Noordman A, Wechselberger R, van den Brink N, Boelens R, et al. Hinge-helix formation and DNA bending in various lac repressor-operator complexes. EMBO J. 1999;18:6472-80 pubmed
- Stoebel D. Lack of evidence for horizontal transfer of the lac operon into Escherichia coli. Mol Biol Evol. 2005;22:683-90 pubmed
- Mettetal J, Muzzey D, Pedraza J, Ozbudak E, van Oudenaarden A. Predicting stochastic gene expression dynamics in single cells. Proc Natl Acad Sci U S A. 2006;103:7304-9 pubmed..Our results provide a proof of principle for the possibility of faithfully predicting dynamic population distributions from deterministic models supplemented by a stochastic component that captures the major noise sources. ..