真核基因表达调控课件

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Eukaryotic Gene Expression,Managing the Complexities of Controlling Eukaryotic Genes,Eukaryotic Gene ExpressionMana,1,Logical,Expression Control Points,(1)DNA packaging,(2)Transcription,(3)RNA processing,(4)mRNA Export,(5)mRNA masking/unmasking and/or modification,(6)mRNA degradation,(7)Translation,(8)Protein modification,(9)Protein transport,(10)Protein degradation,Logical Expression Control Poi,2,DNA,Cytoplasm,Nucleus,G,AAAAAA,Export,Degradation etc.,G,AAAAAA,Control of Gene Expression,G,AAAAAA,RNA,Processing,mRNA,RNA,Transcription,Nuclear,pores,Ribosome,Translation,Packaging,Modification,Transportation,Degradation,DNACytoplasmNucleusGAAAAAAExpo,3,Eukaryotes Have Large Complex Geneomes,The human genome is about 3 x 10,9,base pairs or 1 m of DNA.,Because humans are diploid,each nucleus contains 6 3 x 10,9,base pairs or 2 m of DNA.,That is a lot to pack into a little nucleus!,Eukaryotes Have Large Complex,4,Eukaryotic DNA Must be Packaged,Eukaryotic DNA exhibits many levels of packaging.,The fundamental unit is the nucleosome,and DNA wound around histone proteins.,Nucleosomes arrange themselves together to form higher and higher levels of packaging.,Eukaryotic DNA Must be Package,5,Packaging DNA:Levels of Eukaryotic Chromatin Structure,First level of chromatin coiling,Nucleosome=DNA+histone proteins,Variations in chromatin condensation affect,gene activity,.,Packaging DNA:Levels of Eukar,6,Highly Packaged DNA Cannot be Expressed,(1)The most highly packaged form of DNA is“heterochromatin”.,(2)Heterochromatin cannot be transcribed,therefore expression of genes is prevented.,(3)Chromosome puffs(,胀泡,)on some insect chomosomes illustrate where active gene expression is going on.,Highly Packaged DNA Cannot be,7,Transcriptional Regulation:Effects of Chromatin Structure,Decompaction of chromatin:,Transcription factors unwind nucleosomes in the area where transcription will begin,creating DNAse I hypersensitive sites.,RNA polymerase unwinds more nucleosomes as transcription proceeds.,Transcriptional Regulation:Ef,8,Transcriptional Regulation:Effects of Chromatin Structure,Acetylation(,乙酰化,)of histone proteins(adding-CH,3,CO)reduces DNA-histone interaction,permitting transcription factors to bind.,Transcriptional Regulation:Ef,9,Transcriptional Regulation:Effects of Chromatin Structure,(1)DNA Methylation(adding-CH,3,)can occur on cytosines at CpG groupings near transcription start sites,Inactive genes have methylated cytosines.,Active genes have demethylated cytosines.,(2)Acetylation of histones is associated with cytosine demethylation.,Transcriptional Regulation:E,10,Eukaryotic RNA Polymerase II,RNA polymerase is a very fancy enzyme that does many tasks in conjunction with other proteins.,RNA polymerase II is a protein complex of over 500 kD with more than 10 subunits.,Eukaryotic RNA Polymerase IIRN,11,Eukaryotic RNA Polymerase II Promoters,Several sequence elements spread over about 200 bp upstream from the transcription start site make up RNA Pol II promoters.,Enhancers,in addition to promoters,influence the expression of genes.,Eukaryotic expression control involves many more factors than control in prokaryotes.,This allows much finer control of gene expression.,Eukaryotic RNA Polymerase II P,12,Eukaryotic RNA Polymerase II Promoters,Eukaryotic promoters are made up of a number of sequence elements spread over about 200 bp upstream from the transcription start site.,In addition to promoters,enhancers also influence the expression of genes.,Control of gene expression in eukaryotes involves many more factors than control in prokaryotes.,This allows much finer control of gene expression.,Eukaryotic RNA Polymerase II P,13,A“Simple”Eukaryotic Gene,Terminator,Sequence,Promoter/,Control Region,Transcription,Start Site,3,5,RNA Transcript,Introns,Exon 2,Exon 3,Int.2,Exon,1,Int.1,3 Untranslated Region,5 Untranslated Region,Exons,A“Simple”Eukaryotic GeneTerm,14,Eukaryotic Promoters,Eukaryotic Promoters,15,Response Elements,(1)Response elements are short sequences found either within about 200 bp of the transcription start site,or as part of enhancers.,(2)Different genes have different response elements.,(3)Binding of transcription factors to response elements determines which genes will be expressed in any cell type under any set of conditions.,Response Elements(1)Response,16,5,DNA,3,Enhancers,Enhancer,Transcribed Region,3,5,TF,TF,TF,3,5,TF,TF,TF,5,RNA,RNA,Pol.,RNA,Pol.,Many bases,Promoter,5DNA3EnhancersEnhancerTransc,17,真核基因表达调控课件,18,Transcriptional Regulation:Control of Initiation,Transcriptional Activator Proteins assist in the formation or action of the basal transcription apparatus.,Transcriptional Regulation:Co,19,Transcriptional Regulation:Control of Initiation,Transcriptional Activator Proteins bind to Enhancer sequences that increase transcription,Enhancers can influence promoters at distances of 5