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Introduction to Genetic Analysis
Griffiths • Wessler • Carroll • Doebley Introduction to Genetic Analysis ELEVENTH EDITION CHAPTER 12 Regulation of Gene Expression in Eukaryotes © 2015 W. H. Freeman and Company
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CHAPTER OUTLINE 12.1 Transcriptional regulation in eukaryotes: an overview 12.2 Lessons from yeast: the GAL system 12.3 Dynamic chromatin 12.4 Activation of genes in a chromatin environment 12.5 Long-term inactivation of genes in a chromatin environment 12.6 Gender-specific silencing of genes and whole chromosomes 12.7 Post-transcriptional gene repression by miRNAs
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Overview of transcriptional regulation in Prokaryotes and Eukaryotes
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Question Which of the following statements best describes the ground state for expression of genes in eukaryotic cells? Gene expression is “on” unless specifically inhibited by the binding of repressor proteins. Gene expression is “off” unless specifically turned on by the binding of transcriptional activator proteins. Gene expression is constitutively “on” in heterochromatin but is constitutively “off” in euchromatin. Gene expression is constitutively “off” in heterochromatin but is constitutively “on” in euchromatin.
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Promoter-proximal elements precede the promoter of a eukaryotic gene
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The Gal pathway
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Yeast
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Transcriptional activator proteins bind to UAS elements in yeast
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Transcriptional activator proteins are modular
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Transcriptional activator proteins may be activated by an inducer
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Transcriptional activator proteins recruit the transcriptional machinery
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Question Which of the following is likely to be a functional domain of a transcription factor that activates the expression of specific genes only under the appropriate environmental cues? DNA-binding domain Transcriptional activation domain RNA synthesis domain All of the above a and b
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The structure of chromatin
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Chromatin remodeling exposes regulatory sequences
SWI/SNF-nudges nucleosomes
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Modifications of histone tails by acetylation (A) and methylation (M): histone code
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Page 446: HAT-Histone acetyltransferases and HDACs-Histone deacetylases
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Acetylation of histone tails results in altered chromatin and affect gene expression
Hypoacetylated-inactive gene Hyperacetylation-active gene
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Histone deacetylation can turn off gene transcription
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Page 448: HMTase-Histone methyltransferase; histone methylation associated with inactive genes
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Inheritance of chromatin states
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Page 449
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A model for the inheritance of DNA methylation
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Enhanceosomes help recruit the transcriptional machinery
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Enhanceosomes recruit chromatin remodelers
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Enhancer-blocking insulators prevent enhancer activation
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Model for how enhancer-blocking insulators might work
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Question An enhancer is best described as a:
Specialized DNA sequence that acts to promote expression of specific genes Transcription factor that acts to promote expression of specific genes Binding site for RNA polymerase Protein that binds to RNA polymerase, thereby modulating the rate at which RNA polymerase transcribes a given gene TATA box-containing DNA element
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Spreading heterochromatin can silence genes
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Barrier insulators stop the spread of heterochromatin
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Epigenetics Epigenetics-the study of heritable changes in gene function that do not involve changes in the DNA sequence; literally, over or above traditional genetics Epigenetic changes or “marks” include: Histone acetylation- associated with gene activity Histone methylation- associated with gene inactivity DNA methylation- associated with gene inactivity These epigenetic marks are added by chemicals in your environment (even in utero) and by your behavior (e.g., smoking, diet) and are passed onto your offspring! Specific epigenetic processes include imprinting, gene silencing, X chromosome inactivation, and position effects.
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Epigenetics
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Genomic imprinting requires insulators Maternal imprinting = mother’s allele is inactive Paternal imprinting = father’s allele is inactive
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Unusual inheritance of imprinted genes
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A model for X-chromosome inactivation
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Possible models for the repression of translation by miRNA
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