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Introduction to Genetic Analysis

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1 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

2 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

3 Overview of transcriptional regulation in Prokaryotes and Eukaryotes

4 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.

5 Promoter-proximal elements precede the promoter of a eukaryotic gene

6 The Gal pathway

7 Yeast

8 Transcriptional activator proteins bind to UAS elements in yeast

9 Transcriptional activator proteins are modular

10 Transcriptional activator proteins may be activated by an inducer

11 Transcriptional activator proteins recruit the transcriptional machinery

12 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

13 The structure of chromatin

14 Chromatin remodeling exposes regulatory sequences
SWI/SNF-nudges nucleosomes

15 Modifications of histone tails by acetylation (A) and methylation (M): histone code

16 Page 446: HAT-Histone acetyltransferases and HDACs-Histone deacetylases

17 Acetylation of histone tails results in altered chromatin and affect gene expression
Hypoacetylated-inactive gene Hyperacetylation-active gene

18 Histone deacetylation can turn off gene transcription

19 Page 448: HMTase-Histone methyltransferase; histone methylation associated with inactive genes

20 Inheritance of chromatin states

21 Page 449

22 A model for the inheritance of DNA methylation

23 Enhanceosomes help recruit the transcriptional machinery

24 Enhanceosomes recruit chromatin remodelers

25 Enhancer-blocking insulators prevent enhancer activation

26 Model for how enhancer-blocking insulators might work

27 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

28 Spreading heterochromatin can silence genes

29 Barrier insulators stop the spread of heterochromatin

30 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.

31 Epigenetics

32 Genomic imprinting requires insulators Maternal imprinting = mother’s allele is inactive Paternal imprinting = father’s allele is inactive

33 Unusual inheritance of imprinted genes

34 A model for X-chromosome inactivation

35 Possible models for the repression of translation by miRNA


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