Regulation of gene expression

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lac operon model

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Regulation of gene expression

  1. 1. Regulation of gene expression Dr. N.R.Hazari
  2. 2.  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.
  3. 3.  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.
  4. 4.  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.
  5. 5.  There are two types of gene regulation 1. Positive Regulation 2. Negative regulation.
  6. 6. 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
  7. 7. 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.
  8. 8. 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.
  9. 9.  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.
  10. 10. 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.
  11. 11.  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.
  12. 12. 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.
  13. 13. 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.
  14. 14.  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.
  15. 15. 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.
  16. 16.  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.
  17. 17. Lac Operon regulatory site structural gene I P O Z Y A operator transacetylase promoter permease CAP-binding siteregulatory gene β galactosidase
  18. 18. Metabolism of lactose
  19. 19. 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.
  20. 20. 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
  21. 21. Regulation of lac-operon : glucose ispresent and lactose is absentIN 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.
  22. 22. Situation I I RNA pol P O Z Y AmRNA
  23. 23. Situation II When lactose is present, lacZ, lacY, and lacA genes are expressed. I P O Z RNA pol Y AmRNA galactosidaserepressor allolactose lactose
  24. 24. 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
  25. 25. 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
  26. 26. 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
  27. 27. THANK YOU! RNA pol

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