Gene Regulation and MicroarraysOverviewCells respond to environmentGenome is fixed – Cells are dynamicWhere gene regulation takes placeTranscriptional RegulationTranscription Factors Binding to DNAPromoter and EnhancersRegulation of GenesSlide 10Slide 11Slide 12Slide 13Example: A Human heat shock proteinThe Cell as a Regulatory NetworkThe Cell as a Regulatory Network (2)DNA MicroarraysWhat is a microarraySlide 19Slide 20Slide 21Goal of Microarray ExperimentsClustering vs. ClassificationClustering AlgorithmsHierarchical clusteringDistance between clustersResults of Clustering Gene ExpressionK-Means Clustering AlgorithmK-Means AlgorithmSlide 30Slide 31Slide 32Slide 33Slide 34Slide 35Mixture of Gaussians – Probabilistic K-meansSlide 374. Analysis of Clustering DataEvaluating clusters – Hypergeometric DistributionFinding Regulatory MotifsRegulatory Motif DiscoveryCharacteristics of Regulatory MotifsSequence LogosProblem DefinitionAlgorithmsDiscrete Approaches to Motif FindingDiscrete FormulationsCS262 Lecture 17, Win07, BatzoglouGene Regulation and Gene Regulation and MicroarraysMicroarraysCS262 Lecture 17, Win07, BatzoglouOverview•A. Gene Expression and Regulation•B. Measuring Gene Expression: Microarrays•C. Finding Regulatory MotifsCS262 Lecture 17, Win07, BatzoglouCells respond to environmentCell responds toenvironment—various external messagesCS262 Lecture 17, Win07, BatzoglouGenome is fixed – Cells are dynamic•A genome is staticEvery cell in our body has a copy of same genome•A cell is dynamicResponds to external conditionsMost cells follow a cell cycle of division•Cells differentiate during development•Gene expression varies according to:Cell typeCell cycleExternal conditionsLocationslide credits: M. KellisCS262 Lecture 17, Win07, BatzoglouWhere gene regulation takes place•Opening of chromatin•Transcription•Translation•Protein stability•Protein modificationsCS262 Lecture 17, Win07, BatzoglouTranscriptional Regulation•Efficient place to regulate: No energy wasted making intermediate products•However, slowest response timeAfter a receptor notices a change:1. Cascade message to nucleus2. Open chromatin & bind transcription factors3. Recruit RNA polymerase and transcribe4. Splice mRNA and send to cytoplasm5. Translate into proteinCS262 Lecture 17, Win07, BatzoglouTranscription Factors Binding to DNATranscription regulation:Certain transcription factors bind DNABinding recognizes DNA substrings:Regulatory motifsCS262 Lecture 17, Win07, BatzoglouPromoter and Enhancers•Promoter necessary to start transcription•Enhancers can affect transcription from afarCS262 Lecture 17, Win07, BatzoglouRegulation of Genes GeneRegulatory ElementRNA polymerase(Protein)Transcription Factor(Protein)DNACS262 Lecture 17, Win07, BatzoglouRegulation of Genes GeneRNA polymeraseTranscription Factor(Protein)Regulatory ElementDNACS262 Lecture 17, Win07, BatzoglouRegulation of Genes GeneRNA polymeraseTranscription FactorRegulatory ElementDNANew
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