Regulation of gene expressionPresentation Transcript
Regulation of geneexpressionDr. N.R.Hazari
Gene: A DNA segment that contains theall genetic information required toencodes RNA and protein molecules. Genome: A complete set of genes of agiven species. Gene expression: A process of genetranscription and translation.
Expression of many genes is relativelycontinuous. Some genes are expressed only under certain conditions, nutritional during differentiation and development after physiological stimulations(nervous,Hormonal etc) stressful situations. Thus there is mechanism by which thecells express or turn off certain genes.
High cost of protein synthesis, regulationof gene expression is essential to makingoptimal use of energy. Regulation of gene expression isabsolutely essential for the growth,development, differentiation and veryexistence of an organism.
There are two types of gene regulation 1. Positive Regulation 2. Negative regulation.
Positive regulation The expression of gene isincreased by the presence ofspecific regulatory element ,is saidpositive regulation. The molecule which exert positiveregulation is said to be positiveregulator or activator / inducer The process is called Derepressionor Induction
Negative regulation The expression of gene isdecreased by the presence ofspecific regulatory element ,issaid negative regulation. Molecule which exert the negativeregulation is said to be a negativeregulator or repressor. The process is called Repression.
Sites Gene regulation occurs at thetranscriptional, post-transcriptional,translational and post-translational level. Controlling gene expression is oftenaccomplished by controlling transcriptioninitiation in prokaryotes.
The environmental and metabolic state ofthe cell has a direct and significant effect onthe control of gene expression. Usually small extracellular or intracellularmetabolites trigger the complex mechanisms. (stimulate or inhibit). All genes are not expressed at all time or inall tissues. Ex: Insulin gene expressed only inpancreatic cells but not in other tissues. Thatmeans insulin gene is in repression state inother tissue.
Type of gene expression Genes or gene expression areconsidered under two categories:1. Constitutive genes or expression: Some genes are essential andnecessary for life, and therefore arecontinuously expressed, such as thoseenzymes involved in TCA cycle. Thesegenes are called housekeeping genes.
2. Inducible gene or expressionInduction and repressionThe expression levels of somegenes fluctuate in response to theexternal signals.Ex: Tryptophan pyrrolase inducedby tryptophan.
Prokaryotic gene regulation. Prokaryotes provide models for the study ofgene expression in mammalian cells. Some features of prokaryotes geneexpression are unique. In prokaryotes, genes involved in metabolicpathway are often present in linear arraycalled as OPERON. ( mRNA are polycistronic) Multiple genes are present on singletranscript and a single promoter initiates thetranscription all genes.
OPERONFrancois Jacob & Monod in 1961 firstdescribe operon model in E-coli.An operon is a groupof genes that aretranscribed at thesame time.They usually controlan importantbiochemical process.They are found only inprokaryotes.
Their theory was based on observations oflactose metabolism in E-Coli. When E-Coli cells grown in glucosemedium cells don’t contain β-galactosidaseenzyme. But when cells are transferred to mediumcontain only lactose, then β-galactosidaselevel increases. β-galactosidase hydrolyses the lactose intogalactose & glucose.
Operon The gene for this enzyme isclustered with other two geneswhich produce two enzymes whichare involve in lactose metabolismwith β-galactosidase, i.e.galactoside permease andthiogalactoside transacetylase.
Genes product involve in the samepathway and initiate the transcription ofthese genes by single promoter andregulate by a single gene called operons. Some operons induced when metabolicpathway needed.For prokaryotic systems:Operon is composed of structural genes,promoter, operator, and other regulatorysequences.
Adapting to the environment E. coli can use either glucose, which is amonosaccharide, or lactose, which is adisaccharide. However, lactose needs to be hydrolysed(digested) first. So the bacterium prefers to use glucose whenit can present and its genes are constitutive.
Regulation of Lac -operon Four situations are possible1. When glucose is present and lactose is absentthe E. coli does not produce β-galactosidase.2. When glucose is present and lactose is presentthe E. coli does not produce β-galactosidase.3. When glucose is absent and lactose is absentthe E. coli does not produce β-galactosidase.4. When glucose is absent and lactose is presentthe E. coli does produce β-galactosidase
Regulation of lac-operon : glucose ispresent and lactose is absent IN the absences of lactose, the cell hasno need to produce lactose metabolizingenzymes. Hence lac repressor protein , preventsexpression of genes of lactosemetabolism.
AYZOPImRNARNA polSituation I
Situation IIWhen lactose is present, lacZ, lacY, and lacAgenes are expressed.AYZOPIrepressormRNAlactoseallolactoseRNA polgalactosidase
Situation IIIAYZOPI RNA polWhen glucose is present, the [cAMP] is low, no CAP-cAMP isformed and the expression of the lac operon is still low.
Situation 4AYZOPICAPcAMPRNA polWhen glucose is absent and lactose is present, the CAP-cAMP complex binds to the CAP site to activate the lac gene.