Gene: A DNA segment that contains the all genetic information required to encodes RNA and protein molecules. Genome: A complete set of genes of a given species. Gene expression: A process of gene transcription and translation.
Expression of many genes is relatively continuous. 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 the cells express or turn off certain genes.
High cost of protein synthesis, regulation of gene expression is essential to making optimal use of energy. Regulation of gene expression is absolutely essential for the growth, development, differentiation and very existence of an organism.
There are two types of gene regulation 1. Positive Regulation 2. Negative regulation.
Positive regulation The expression of gene is increased by the presence of specific regulatory element ,is said positive regulation. The molecule which exert positive regulation is said to be positive regulator or activator / inducer The process is called Derepression or Induction
Negative regulation The expression of gene is decreased by the presence of specific regulatory element ,is said negative regulation. Molecule which exert the negative regulation is said to be a negative regulator or repressor. The process is called Repression.
Sites Gene regulation occurs at the transcriptional, post-transcriptional, translational and post-translational level. Controlling gene expression is often accomplished by controlling transcription initiation in prokaryotes.
The environmental and metabolic state of the cell has a direct and significant effect on the control of gene expression. Usually small extracellular or intracellular metabolites trigger the complex mechanisms. (stimulate or inhibit). All genes are not expressed at all time or in all tissues. Ex: Insulin gene expressed only in pancreatic cells but not in other tissues. That means insulin gene is in repression state in other tissue.
Type of gene expression Genes or gene expression are considered under two categories: 1. Constitutive genes or expression: Some genes are essential and necessary for life, and therefore are continuously expressed, such as those enzymes involved in TCA cycle. These genes are called housekeeping genes.
2. Inducible gene or expression Induction and repression The expression levels of some genes fluctuate in response to the external signals. Ex: Tryptophan pyrrolase induced by tryptophan.
Prokaryotic gene regulation. Prokaryotes provide models for the study of gene expression in mammalian cells. Some features of prokaryotes gene expression are unique. In prokaryotes, genes involved in metabolic pathway are often present in linear array called as OPERON. ( mRNA are polycistronic) Multiple genes are present on single transcript and a single promoter initiates the transcription all genes.
OPERON Francois Jacob & Monod in 1961 first describe 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 of lactose metabolism in E-Coli. When E-Coli cells grown in glucose medium cells don’t contain β-galactosidase enzyme. But when cells are transferred to medium contain only lactose, then β-galactosidase level increases. β-galactosidase hydrolyses the lactose into galactose & glucose.
Operon The gene for this enzyme is clustered with other two genes which produce two enzymes which are involve in lactose metabolism with β-galactosidase, i.e. galactoside permease and thiogalactoside transacetylase.
Genes product involve in the same pathway and initiate the transcription of these genes by single promoter and regulate by a single gene called operons. Some operons induced when metabolic pathway needed.For prokaryotic systems:Operon is composed of structuralgenes, promoter, operator, and other regulatorysequences.
Lac Operon regulatory site structural gene I P O Z Y A operator transacetylase promoter permease CAP-binding siteregulatory gene β galactosidase
Adapting to the environment E. coli can use either glucose, which is a monosaccharide, or lactose, which is a disaccharide. However, lactose needs to be hydrolysed (digested) first. So the bacterium prefers to use glucose when it can present and its genes are constitutive.
Regulation of Lac -operon Four situations are possible1. When glucose is present and lactose is absent the E. coli does not produce β-galactosidase.2. When glucose is present and lactose is present the E. coli does not produce β-galactosidase.3. When glucose is absent and lactose is absent the E. coli does not produce β-galactosidase.4. When glucose is absent and lactose is present the E. coli does produce β-galactosidase
Regulation of lac-operon : glucose ispresent and lactose is absentIN the absences of lactose, the cell has no need to produce lactose metabolizing enzymes. Hence lac repressor protein , prevents expression of genes of lactose metabolism.
Situation II When lactose is present, lacZ, lacY, and lacA genes are expressed. I P O Z RNA pol Y AmRNA galactosidaserepressor allolactose lactose
Situation IIIWhen glucose is present, the [cAMP] is low, no CAP-cAMP isformed and the expression of the lac operon is still low. I RNA pol P O Z Y A
Situation 4When glucose is absent and lactose is present, the CAP-cAMP complex binds to the CAP site to activate the lac gene.cAMP CAP I RNA pol P O Z Y A
SummaryCarbohydrate Activator Repressor RNA lac Operon s protein protein polymeras e + GLUCOSE Not bound Lifted off Keeps falling No + LACTOSE to DNA operator site off promoter transcription site + GLUCOSE Not bound Bound to Blocked by No - LACTOSE to DNA operator site the repressor transcription - GLUCOSE Bound to Bound to Blocked by No - LACTOSE DNA operator site the repressor transcription - GLUCOSE Bound to Lifted off Sits on the Transcription + LACTOSE DNA operator site promoter site