ActivatorproteinsInteract with other proteins to activate and increasetranscriptionabovebasallevelsAlsocalledtranscriptionfactors.Two structural domains mediate these functions:DNA-binding domain, bind to enhancer DNA in specific waysTranscription-activating domainDimerizationdomainADDNA-binding美Gal4domainDNA-bindingRNAdomainTranscriptionPolDBDXGALIUASG(UpstreamActivatingCGGnnnnnnnnnnnCCGSequence)(17 bp Gal4-binding site)18-16
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-16 Activator proteins Activator proteins Interact with other proteins to activate and increase Interact with other proteins to activate and increase transcription above basal levels. transcription above basal levels. Also called Also called transcription factors. transcription factors. Two structural domains mediate these functions: Two structural domains mediate these functions: DNA-binding domain, bind to enhancer DNA in specific ways. binding domain, bind to enhancer DNA in specific ways. Transcription Transcription-activating domain activating domain RNA Pol. Transcription UASG (Upstream Activating Sequence) AD Gal4 DBD GAL1 RNA Pol. Transcription UASG (Upstream Activating Sequence) AD Gal4 DBD GAL1 CGGnnnnnnnnnnnCCG (17 bp Gal4-binding site) Dimerization domain DNA-binding domain DNA-binding domain CGGnnnnnnnnnnnCCG (17 bp Gal4-binding site) Dimerization domain DNA-binding domain DNA-binding domain
Basal factorsandpol IEnhancerDNATATATranscriptionalLow-leveltranscriptionactivatorsbindtooccurswithonlybasalspecific enhancersfactorboundto DNA.atspecifictimestoBasalfactorsandpollincreasetranscriptionalTATAWhenbasallevels.factorandactivatorareboundtoDNA,rateofEnhancerDNAtranscriptionincreases.Activatorprotein(b)ActivatorsrecruitcoactivatorsthatdisplacenucleosomesCoactivatorActivatorEnhancerPromoterFig.16.6
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-17 Transcriptional Transcriptional activators activators bind to bind to specific enhancers specific enhancers at specific times to at specific times to increase increase transcriptional transcriptional levels. levels. Fig. 16.6
The locus control region (LCR) is a cis-acting regulatorysequence that operates sequentially on a cluster of relatedgenesHemegroupFig.9.la, bHuman β-globin gene cluster contains five genes that can all beregulatedbyadistantLCR(locus control region),5okbupstreamofβ-globingene.010203040506070kb1HS4HS3HS2HS1BGyAyBo8HHLCRChrr.11
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-18 The locus control region (LCR) is a The locus control region (LCR) is a cis-acting regulatory acting regulatory sequence that operates sequentially on a cluster of related sequence that operates sequentially on a cluster of related genes Human -globin gene cluster contains five genes that can all be gene cluster contains five genes that can all be regulated by a distant regulated by a distant LCR (locus control region), 50 kb (locus control region), 50 kb upstream of upstream of -globin gene. Chr. 11 Fig. 9.1a, b
88BGYAyLCRHS54321~15kbpJ-60kbpadultembryonicGlobin gene expressionfetalliverbonemarrowyolk sacduring human developmentaeo50Y430208Sβ10-0624303642012182430612184836Birth(c)Weeksofdevelopment18-19
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-19
LCR is needed for activation of β-globin gene(b)TransgeneRegionbetweengenesTransgene inmice failstobe transcribedatproperlevels,thereforethere is a missing cis-actingEdgeofβ-globinregulatory element.nextgenegene18-20
Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display 18-20 LCR is needed for activation of LCR is needed for activation of -globin gene