Overview: Conducting the Genetic OrchestraPowerPoint PresentationOperons: The Basic ConceptSlide 4Slide 5Slide 6Concept 18.2: Eukaryotic gene expression can be regulated at any stageSlide 8Regulation of Chromatin StructureSlide 10DNA MethylationConcept 18.3: Noncoding RNAs play multiple roles in controlling gene expressionSlide 13Concept 18.5: Cancer results from genetic changes that affect cell cycle controlTumor-Suppressor GenesSlide 16Slide 17The Multistep Model of Cancer DevelopmentCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsOverview: Conducting the Genetic Orchestra•Prokaryotes and eukaryotes alter gene expression in response to their changing environment•In multicellular eukaryotes, gene expression regulates development and is responsible for differences in cell types•RNA molecules play many roles in regulating gene expression in eukaryotes•In Prokaryotes, natural selection has favored bacteria such that they produce only the products needed by that cell•A Prokaryotic cell can regulate the production of enzymes by feedback inhibition or by gene regulation•Gene expression in bacteria is controlled by the operon modelFig. 18-2Regulationof geneexpressiontrpE genetrpD genetrpC genetrpB genetrpA gene(b) Regulation of enzyme production(a) Regulation of enzyme activityEnzyme 1Enzyme 2Enzyme 3TryptophanPrecursorFeedbackinhibitionCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsOperons: The Basic Concept•A cluster of functionally related genes can be under coordinated control by a single on-off “switch”•The regulatory “switch” is a segment of DNA called an operator usually positioned within the promoter•An operon is the entire stretch of DNA that includes the operator, the promoter, and the genes that they control•The operon can be switched off by a protein repressor•The repressor prevents gene transcription by binding to the operator and blocking RNA polymerase•The repressor is the product of a separate regulatory geneFig. 18-3aPolypeptide subunits that make upenzymes for tryptophan synthesis(a) Tryptophan absent, repressor inactive, operon onDNAmRNA 5Protein InactiverepressorRNApolymeraseRegulatorygenePromoterPromotertrp operonGenes of operonOperatorStop codonStart codonmRNAtrpA53trpR trpEtrpDtrpC trpBABCDEE. coli can synthesize the amino acid tryptophan. By default the trp operon is on and the genes for tryptophan synthesis are transcribedFig. 18-3b-1(b) Tryptophan present, repressor active, operon offTryptophan(corepressor)No RNA madeActiverepressormRNAProteinDNAA corepressor is a molecule that cooperates with a repressor protein to switch an operon offFig. 18-3b-2(b) Tryptophan present, repressor active, operon offTryptophan(corepressor)No RNA madeActiverepressormRNAProteinDNAWhen tryptophan is present, it binds to the trp repressor protein, which turns the operon off The repressor is active only in the presence of its corepressor tryptophan; thus the trp operon is turned off (repressed) if tryptophan levels are highCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsConcept 18.2: Eukaryotic gene expression can be regulated at any stage•All organisms must regulate which genes are expressed at any given time•In multicellular organisms gene expression is essential for cell specialization•Almost all the cells in an organism are genetically identical•Differences between cell types result from differential gene expression, the expression of different genes by cells with the same genome•Errors in gene expression can lead to diseases including cancer•Gene expression is regulated at many stagesFig. 18-6DNASignalGeneNUCLEUSChromatin modificationChromatinGene availablefor transcriptionExonIntronTailRNACapRNA processingPrimary transcriptmRNA in nucleusTransport to cytoplasmmRNA in cytoplasmTranslationCYTOPLASMDegradationof mRNAProtein processingPolypeptideActive proteinCellular functionTransport to cellulardestinationDegradationof proteinTranscriptionCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsRegulation of Chromatin Structure•Genes within highly packed heterochromatin are usually not expressed•Chemical modifications to histones and DNA of chromatin influence both chromatin structure and gene expression•In histone acetylation, acetyl groups are attached to positively charged lysines in histone tails•This process loosens chromatin structure, thereby promoting the initiation of transcription•The addition of methyl groups (methylation) can condense chromatin; the addition of phosphate groups (phosphorylation) next to a methylated amino acid can loosen chromatinCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsFig. 18-7HistonetailsDNAdouble helix(a) Histone tails protrude outward from a nucleosomeAcetylated histonesAminoacidsavailablefor chemicalmodification(b) Acetylation of histone tails promotes loose chromatin structure that permits transcriptionUnacetylated histonesCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsDNA Methylation•DNA methylation, the addition of methyl groups to certain bases in DNA, is associated with reduced transcription in some species•DNA methylation can cause long-term inactivation of genes in cellular differentiation•In genomic imprinting, methylation regulates expression of either the maternal or paternal alleles of certain genes at the start of developmentCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin CummingsConcept 18.3: Noncoding RNAs play multiple roles in controlling gene expression•Only a small fraction of DNA codes for proteins, rRNA, and tRNA•A significant amount of the genome may be transcribed into noncoding RNAs•Noncoding RNAs regulate gene expression at two points: mRNA translation and chromatin configuration1. The noncoding RNAs that regulate mRNA translation are MicroRNAs (miRNAs) , these are small single-stranded RNA molecules that can bind to mRNA•These can degrade mRNA or block its translationCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings2. The noncoding RNAs that regulate chromatin configration are small interfering RNAs (siRNAs) , these are small double-stranded RNA molecules that can bind to and block large regions of the chromosome•Both of these miRNAs and siRNAs inhibit gene expression by targeting the