BIOL 118 1st Edition Lecture 18 Outline of Last Lecture I Introduction II Gene Regulation Information Flow III Mechanisms of Regulation An Overview IV Transcriptional Control of Gene Expression V Translation Control of Gene Expression VI Post Translational Control of Gene Expression VII Control of Gene Expression in Bacteria VIII Metabolizing Lactose A Model System IX Identifying Genes Under Regulatory Control X Finding Mutants for a Particular Trait XI Replica Plating to Find Mutant Genes XII Different Classes of Lactose Metabolism Mutants XIII Several Genes Are Involved in Metabolizing Lactose XIV Transcriptional Regulation XV Mechanisms of Negative Control The Repressor XVI The lac Operon XVII How Does Glucose Regulate the lac Operon XVIII Why Has the lac Operon Model Been So Important Outline of Current Lecture I Differential Gene Expression II Mechanisms of Gene Regulation An Overview III Three Additional Levels Unique to Eukaryotes IV What is Chromatin s Basic Structure V Chromatin Structure is Altered in Active Genes VI Negative Control of Eukaryotic Genes VII How is Chromatin Altered VIII Chromatin Modifications Can Be Inherited IX How Is Transcription Occurring in Eukaryotic Cells And How Might It Be Regulated X Characteristics of Enhancers XI Enhancers Silencers XII What Role Do Regulatory Proteins Play XIII Types of Transcription Factors XIV The Mediator Complex XV Transcription Initiation in Eukaryotic Cells XVI Post Transcriptional Control These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute XVII XVIII Post Translational Control Comparing Gene Expression in Bacteria Eukaryotes Current Lecture Differential Gene Expression Responsible for creating different cell types Arranging them into tissues Coordinating their activity Forms the multicellular society we call an individual Mechanisms of Gene Regulation An Overview Eukaryotes like prokaryotes can control gene expression at the levels of o Transcription o Translation o Post translation Three Additional Levels of Control Unique to Eukaryotes Chromatin Remodeling o In eukaryotes DNA is wrapped around proteins to create a protein DNA complex called chromatin RNA polymerase cannot access the DNA when it is supercoiled within the nucleus o DNA near the promoter is released from tight interactions with proteins decondensed occurs before transcription RNA Processing Control of mRNA stability o Transcription results in a primary RNA transcript Must undergo RNA processing to produce a mature mRNA Introns snipped exons spliced o mRNA stability how long it will live The life span of an mRNA mature transcript can be a control point for gene expression If short lived won t produce many protein products If longer life will produce more protein products What is Chromatin s Basic Structure Chromatin has a regular structure with several layers of organization Contains nucleosomes repeating beadlike structures o Consist of negatively charged DNA wrapped twice around eight positively charged histone proteins o Histone protein called H1 functions to maintain the structure of each nucleosome May also interact with each other and other histones in other nucleosomes to form a tightly packed structure called a 30 nanometer fiber form higher order structures o Between each pair of nucleosomes there is a linker stretch of DNA Chromatin s elaborate structure allows the DNA to be packaged in the nucleus plays a key role in regulating gene expression Chromatin Structure Is Altered in Active Genes As in bacteria eukaryotic DNA has sites called promoters where RNA polymerase binds to initiate transcription For RNA polymerase to bind to the promoter chromatin must be relaxed or decondensed Negative Control of Eukaryotic Genes The default state of eukaryotic genes is to be turned off o Chromatin is in condensed form o Promoter region isn t available This is a mechanism of negative control A form of positive control must be at work to open up DNA at promoter regions for gene expression to occur How Is Chromatin Altered Two major types of protein are involved in modifying chromatin structure o ATP dependent chromatin remodeling complexes Reshape chromatin o Other enzymes catalyze Acetylation addition of acetyl groups Usually associated with the activation of genes Reduced the positive charge on the histones decondensing the chromatin and allowing gene expression Histone acetyl transferases HATs enzyme adds negatively charged acetyl groups to positively charged lysine residues in histones Histone deacetylases HDACs enzyme that removes the acetyl groups from histones reverse the effects of acetylation allow chromatin condensation Methylation addition of methyl groups Correlated with either activation or inactivation Chromatin Modifications Can Be Inherited Epigenetic Inheritance Patterns of inheritance not due to difference in gene sequences Histone Code Hypothesis Patterns of chemical modifications of histones contain information that influences whether a particular gene is expressed o The pattern of chemical modifications on histones varies from one cell type to another o Daughter cells inherit patterns of histone modifications from the parent cell epigenetic inheritance How Is Transcription Occurring in Eukaryotic Cells And How Might It Be Regulated Regulatory Sequences and Regulatory Proteins Eukaryotic promoters are similar to bacterial promoters o There are 3 conserved sequences o Each eukaryotic promoter has 2 of the 3 o The most common sequence is the TATA box o All eukaryotic promoters are bound by the TATA binding protein TBP Regulatory Sequences Sections of DNA involved in controlling the activity of genes when they bind to these sequences gene activity changes Some regulatory genes are near the promoter o Co regulated genes are not clustered together o Share a regulatory DNA sequence o Binds the same regulatory protein Promoter proximal elements o Located just upstream of the promoter and transcription start site o Have sequences that are unique to specific genes o Provide a mechanism for eukaryotic cells to exert precise control over transcription Characteristics of Enhancers All eukaryotes have enhancers o Can be more than 100 000 bases away from promoter o Can be located in introns o Untranscribed 5 or 3 sequences flanking the gene they regulate Many types of enhancers Many genes have more than one Can work even if their normal orientation
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