Lecture 12 Chapter 11 - Introduction to Genetic Analysis...

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  1 Introduction to Genetic Analysis Ninth Edition Anthony J. F. Griffiths, Susan R. Wessler, Richard C.  Lewontin, and Sean B. Carroll CHAPTER 11 Regulation of Gene Expression in Eukaryotes Copyright 2008 © W H Freeman and Company
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  2 Today’s 4-5 pm office hours changed  to Tomorrow October 5, 4-5pm.
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  3 Gene: Prokaryotes vs. Eukaryotes Eukaryotes One  GENE  One transcriptional unit  One mRNA  One protein. Prokaytoes One  OPERON  One transcriptional unit  One to several coordinately regulated mRNAs Many proteins.
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  4 Transcription Regulation 1. Needed to control 1. How much protein is made – expression levels 2. When – time in development 3. Where – tissue/cell type 1. Can occur 1. At the level of transcription – most common 2. At the level of splicing or processing 3. Post-transcriptional stability – common-miRNA-mediated 4. At the level of translation 5. At the level of protein stability –ubiquitin system 6. At the level of protein modification
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  5 Transcription Regulation Rely on the cooperation of  Cis-acting DNA elements  Trans-acting proteins To facilitate or inhibit binding of RNA polymerase II to  promoters. Activators facilitate binding Repressors inhibit binding
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  6 Transcription Regulation: Eukaryotes vs. prokaryotes Transcriptome = total number of genes Eukaryotes - human = 30,000 Prokaryotes – bacteria = 1000 Eukaryotes Majority of genes in the OFF state (SILENCED). Must control when and where (temporal and spatial control). Thousands of complex gene expression patterns Achieved with a small number of regulatory elements
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  7 Strategies Used Eukaryotes 1. Delegation of duties to more than 1 RNA polymerase. 1. De-coupled transcription and translation. 1. RNA transcription, processing, splicing, stability. 1. Protein  translation, modification, stability. 1. Increased repertoire of cis-acting elements and trans-acting factors  through combinatorial interactions. 1. Chromatin re-modelling.
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  8 Strategies Used Eukaryotes 1. RNA polymerases 1. Prokaryotes – RNA polymerase holoenzyme 2. Eukaryotes –  1. RNA pol I – rRNA (excluding 5S RNA) 2. RNA pol II – mRNA 3. RNA pol III – tRNA, snRNA, 5S RNA 1. RNA processing 1. Prokaryotes – Primary RNA transcript is translated 2. Eukaryotes – Primary transcript undergoes extensive processing. 1. 5’ (CAP) and 3’ (polyA) end modification 2. Intron splicing 3. mRNA is synthesized by RNA pol II which is large and complex in order  to co-ordinate processing events and regulation.
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