Positive Control• Regulation of geneexpression by aregulatory proteincalled activatorprotein.• Activator protein –allows transcriptionNegative Control• Regulation of geneexpression by aregulatory proteincalled repressorprotein.• Repressor protein –hinders transcription
Types of Genes(based on the small effector molecules)Inducible Genes• Genes that are transcriptionallyregulated by an inducer.• Inducer – a small effectormolecule that binds to:– an activator protein whichallows binding of the proteinto the DNA.– A repressor protein whichhinders binding of the proteinto the DNA.Repressible Genes• Genes that are transcriptionallyregulated either by a corepressor oran inhibitor.• Corepressor – a small effectormolecule which binds to arepressor protein that allowsbinding of the protein to the DNA.• Inhibitor – a small effectormolecule which binds to anactivator protein that restrictsbinding of the protein to the DNA.
Definition and DiscoveryDefinition• Refers to two or morecontigious genes and thegenetic elements thatregulate their transcriptionin a coordinate fashion• Consists ofpromoter, operator, andstructural genes• Encodes proteins (enzymes)that have common functionDiscovery• François Jacob and JacquesMonod (1940)• Via combination ofbiochemical and geneticanalyses
Lactose operon• First operon to be discovered• François Jacob and Jacques Monod (1940)• Contains three genes that codes for proteinsinvolved in lactose metabolism in Escherichiacoli that plays a role in bacterial growth• It is said to be inducible– Due to its inducer “Lactose”
Components of the Lac Region• Regulatory gene (LacI)– Expresses the Lac repressor• A regulatory protein of Lac Operon• Responsible for the Negative Control of Lac Operon• Lac Operon– CAP site• The binding site of CAP– Catabolite Activator Protein– Another regulatory protein of Lac Operon– Responsible for the Positive Control of lac Operon
(Continuation)– LacP• Binding site of RNA Polymerase– LacO• Binding site of Lac repressor– LacZ• Encodes β-galactosidase– LacY• Encodes lactose permease– LacA• Encodes galactoside transacetylase
Lactose metabolism in Escherichiacoli• Involves the three enzymes expressed by the lac operon– β-galactosidase• Catalyzes Lactose → Glucose + Galactose• Catalyzes Lactose → Allolactose (side reaction)– Lactose permease• Serves as the channel protein of lactose to the cell– Galactoside transacetylase• Acetylation of lactose and lac analogs
Negative Control• Allosteric regulation• Lac Repressor– Responsible for the negative control of lac operon– Presence of lactose and lac analogs• Binding to the allosteric site• Conformational change in the active site• Hindrance of lac repressor binding• Transcription occurs– Absence of lactose and lac analogs• Binding of lac repressor = No Transcription
Positive Control• Catabolite repression• CAP– Catabolite Activator Protein• Responsible for the positive control of lac operon• Activated by cAMP (Cyclic Adenosine Monophosphate)• Can be deactivated by glucose– Inhibits adenylyl cyclase via glucose transport and asignalling pathway– Adenylyl cyclase catalyzes the conversion of ATP to cAMP
References• Weaver RF. 2012. Molecular Biology 5thEd. New York: McGraw-Hill. 914 P.• Karp G. 2010. Cell and Molecular Biology:Concepts and Experiments 6th ed. NewJersey: John Wiley & Sons, Inc. 837 P.• Brooker RJ. 2012. Genetics: Analysis &Principles 4th Ed. New York: McGraw-Hill.868 P.