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Lecture.19.Fall.2013 - Gene Regulation Mutation and DNA...

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Gene Regulation Mutation and DNA repair November 4, 2013 Gene regulation in prokaryotes (Chapter 16) The trp operon Gene Regulation in Eukaryotes (Chapter 17) - Chromatin Structure - Histone modifications - Epigenetic effects - Control of Transcription - Promoters - Enhancers - Transcription Factors RNA Processing - alternative splicing - RNA interference - Translation and protein modification
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Lecture 14: Gene Regulation Mutation and DNA repair July 30, 2013 Gene Mutations (Chapter 18) Additional (optional, but fun and useful) reading: The Salvation of Doug, by Bill Sullivan tinman , a gene that controls heart development in flies and humans The study of mutations leads to an understanding of gene function Importance of mutations Categories of mutations Phenotypic effects of mutations
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The trp operon of E. coli
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The trp operon is also regulated by attenuation Attenuation: premature termination of transcription
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Attenuation occurs in the presence of tryptophan
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Attenuation occurs in the presence of tryptophan
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Attenuation Why does attenuation take place in the trp operon? Repression only reduces transcription as much as 70-fold Attenuation can further reduce transcription another 8- to 10-fold Together the two processes reduce transcription more than 600-fold
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Antisense RNA can also regulate transcription micF regulates ompF at the translational level
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Prokaryotic Gene Expression: Generalities Genes can be induced or repressed in response to specific environmental conditions Gene expression can be regulated negatively (through repression) or positively (through activation) Secondary structure of DNA and RNA can be used to regulate gene expression
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Eukaryotic Gene Expression All the general mechanisms of prokaryotic regulation are used in eukaryotes The eukaryotic system is more complex More potential levels of regulation Much larger genome, with many associated proteins (histones, etc.)
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Eukaryotic Gene Expression Transcription and translation are separated Transcripts are extensively processed (capping, poly-A tail, splicing) mRNA is much more stable Allows extensive translational control
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Levels of Control of Eukaryotic Gene Expression Chromatin Structure Histone modifications Epigenetic effects Transcriptional Promoters and enhancers
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Levels of Control of Eukaryotic Gene Expression mRNA processing Splicing Translational control 5’ and 3’ UTRs Post-translational regulation phosphorylation
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Changes in chromatin structure affect gene expression Chromatin structure becomes more open for gene expression At least four mechanisms: Histone methylation Histone acetylation Chromatin-remodeling complexes DNA methylation
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Histone Methylation Addition of methyl groups to histone tails Can lead to activation or repression, depending on which amino acid is methylated Example: H3K4me3 (3 methyl groups added to lysine 4 of histone 3)
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H3K4me3 recruits NURF NURF = nucleosome remodeling factor Recognizes and binds to H3K4me3 and and alters chromatin packing (making it “looser”)
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