武汉大学：《遗传学》课程教学课件（英文讲稿）Chapter 16 Gene Regulation in Eukaryotes

Chapter 16Gene Regulation in Eukaryotes18-1

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Sectionsto study16.1Overview of eukaryoticgene regulation16.2 Control of transcription initiation through promoters andenhancers16.3 Epigenetics: Control of transcription initiation throughDNAmethylation16.4Regulation after transcription18-2

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-2 Sections to study Sections to study 16.1 Overview of eukaryotic gene regulation 16.1 Overview of eukaryotic gene regulation 16.2 Control of transcription initiation through promoters and 16.2 Control of transcription initiation through promoters and enhancers enhancers 16.3 Epigenetics Epigenetics: Control of transcription initiation through : Control of transcription initiation through DNA methylation methylation 16.4 Regulation after transcription 16.4 Regulation after transcription

DNA16.1 Overview ofI Initiation of transcriptioneukaryoticgenePrimaryRNAtranscriptsregulationTranscriptprocessing(splicing,polyadenylation,5capaddition)Mature RNA transcriptAAAA5'caplExportfromnucleusITranslationProtein productsModifications+LocalizationProteinactionFig.16.1

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Differences of gene regulation inChromatinNucleuseukaryotes compared with(DNA-proteincomplex)1.Chromatinremodelingprokaryotes0"Open"DNA(someDNAnotclosely2.Transcriptionboundtoproteins)Eukaryoticgenomes carry farmoreDNAPrimary transcriptchallenging for proteins to locate binding(pre-mRNA)3.RNAprocessingsequences.TailCapMature mRNAChromatin structure makes DNACytoplasmunavailable to transcription machinery.4.mRNA stabilityAdditional RNA processing events occur.Transcription and translation are spatiallyDegradedmRNAseparated.(mRNAlifespan5.Translationvaries)mRNA-Gene regulation needs to control cellulardifferentiation into hundreds of specializedPolypeptide6,Post-translationalmodification(folding,cell types.glycosylation,transport,activationdegradation ofActiveproteinprotein)2011Pearson Education,Inc

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-4 Differences of gene regulation in eukaryotes compared with prokaryotes  Eukaryotic genomes carry far more DNA, Eukaryotic genomes carry far more DNA, challenging for proteins to locate binding challenging for proteins to locate binding sequences. sequences.  Chromatin structure makes DNA Chromatin structure makes DNA unavailable to transcription machinery. unavailable to transcription machinery.  Additional RNA processing events occur. Additional RNA processing events occur.  Transcription and translation are spatially Transcription and translation are spatially separated. separated.  Gene regulation needs to control cellular Gene regulation needs to control cellular differentiation into hundreds of specialized differentiation into hundreds of specialized cell types. cell types

TABLE18.1KeyRegulatoryDifferences BetweenEukaryotesandProkaryotesProkaryoteEukaryoteCharacteristicYesYesControloftranscriptionthroughspecificDNA-bindingproteinsYesYesReutilizationofsameDNA-bindingmotifsbydifferentDNA-bindingproteinsYesYesActivatorproteinsYesYesRepressorproteinsSpecificSpecificityofbindingtoDNAbyregulatoryproteinHighlyspecificStrongVerystrongAffinityofbindingNoYesRoleplayedbychromatinstructureYesRareCoordinatecontrolachievedwithoperonsNoYesDifferential splicingYesNoAttenuationNoYesmRNAprocessingNoYesDifferentialpolyadenylationNoYesDifferentialtransportofRNAfromnucleustocytoplasmNoYesRNAinterferencecarriedoutbymicro-RNAs18-5

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In eukaryotes, three RNA polymerases transcribe different sets ofgenes.RNA polymeraseI(a)Tandemrepeatsof rRNAgenes aretranscribedbyRNApolymerasel.transcribesrRNARNApolrRNAgenesPromoterTranscriptionrRNAsaremade-?oftandem repeatsononeormorePrimaryrRNAtranscriptschromosomes.RNA polymeraseISubsequentprosessing28SrRNA5.8SrRNA18SrRNAtranscribes oneinnucleolusprimary rRNAtranscript which isfurther processedSmallLargeto 28S, 5.8S, andribosomalribosomalsubunitsubunit18S rRNA.Ribosome18-6

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-6  RNA polymerase I RNA polymerase I transcribes transcribes rRNA.  rRNAs are made are made of tandem repeats of tandem repeats on one or more on one or more chromosomes. chromosomes.  RNA polymerase I RNA polymerase I transcribes one transcribes one primary primary rRNA transcript which is transcript which is further processed further processed to 28S, 5.8S, and to 28S, 5.8S, and 18S rRNA. In eukaryotes, three In eukaryotes, three RNA polymerases RNA polymerases transcribe different sets of transcribe different sets of genes

RNA polymeraseIItranscribes all protein-and micro-RNA-encodinggenes.The cis-acting regulatoryregions of RNA pol.Il-transcribed genescontain promoters and enhancers.(c)Protein-encodingandmicro-RNA-encodinggenesaretranscribedbyRNApolllRNApol IITranscriptionfactorsExonIntronExonIntronExonLPromoterEnhancer-PrimaryRNAtranscriptProcessedmRNATAAAAA5'capPolypeptide productD18-7

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-7  RNA polymerase II RNA polymerase II transcribes all protein transcribes all protein- and micro and micro-RNA￾encoding genes. encoding genes.  The cis-acting regulatory regions of RNA acting regulatory regions of RNA pol. II-transcribed genes transcribed genes contain contain promoters promoters and enhancers enhancers

RNA polymerase III transcribes tRNAs and other small RNAs(5SrRNA,SnRNAs)(b)SmallRNAgenesaretranscribedbyRNApol IlltRNAgenesRNApol II5SRNAgeneTranscriptionunitPromoterPromoter18-8

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-8  RNA polymerase III RNA polymerase III transcribes transcribes tRNAs and other small and other small RNAs (5S rRNA, snRNAs)

16.2 Control of transcription initiation throughpromoters and enhancersProteins act in trans, but DNA sites act only in cis. Cis-acting elements:Short DNA sequences that constitute thecontrol elements adjacent to genes.They can onlyinfluencethe expression of adjacent genes on the same DNA moleculeTrans-acting elements: Genes that code for DNA-bindingproteins. Their protein products can diffuse throughcytoplasm and act at target DNA sites on any DNA moleculeinthecell.18-9

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-9 Proteins act in Proteins act in trans, but DNA sites act only in , but DNA sites act only in cis.  Cis-acting elements acting elements: Short DNA sequences that constitute the : Short DNA sequences that constitute the control elements adjacent to genes. They can only influence control elements adjacent to genes. They can only influence the expression of adjacent genes on the same DNA molecule. the expression of adjacent genes on the same DNA molecule.  Trans-acting elements acting elements: Genes that code for DNA : Genes that code for DNA-binding binding proteins. Their protein products can diffuse through proteins. Their protein products can diffuse through cytoplasm and act at target DNA sites on any DNA molecule in cytoplasm and act at target DNA sites on any DNA molecule in the cell. the cell. 16.2 Control of transcription initiation through 16.2 Control of transcription initiation through promoters and enhancers promoters and enhancers

Cis-acting elements of a genePromoter（启动子）：DNAseguencesnearthebeginningofgenesthat signal RNA polymerase where to begin transcription Promoters contain initiation site andTATA box.Enhancer（增强子）:DNA sequences thataugmentorrepressbasal levels of transcriptionfrom nearby genes DNA sequences that bind transcription factorsCan liefarwayfromgeneCan bereversedTranscriptioncis-actingelements ofagenestart siteRTranscribedEnhancerPromoterregionAPromoterTranscribedEnhancerregion18-10Fig.16.2

Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-10 Cis-acting elements of a gene acting elements of a gene  Promoter ( Promoter (启动子): DNA sequences near the beginning of genes : DNA sequences near the beginning of genes that signal RNA polymerase where to begin transcription. that signal RNA polymerase where to begin transcription.  Promoters contain initiation site and TATA box. Promoters contain initiation site and TATA box.  Enhancer ( Enhancer (增强子): DNA sequences that augment or repress DNA sequences that augment or repress basal levels of transcription from nearby genes. basal levels of transcription from nearby genes.  DNA sequences that bind transcription factors. DNA sequences that bind transcription factors.  Can lie far way from gene. Can lie far way from gene.  Can be reversed. Can be reversed. Fig. 16.2