Week 7 Course Notes: Chapters 18 and 19
Week 7 Course Notes: Chapters 18 and 19 Biol 2002
U of M
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This 6 page Class Notes was uploaded by Sydney Diekmann on Thursday October 15, 2015. The Class Notes belongs to Biol 2002 at University of Minnesota taught by Dr. Susan Wick, Dr. David Matthes in Fall 2015. Since its upload, it has received 30 views. For similar materials see Foundations of Biology in Biology at University of Minnesota.
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Date Created: 10/15/15
Chapter 18 Control of Gene Expression in Bacteria gene expression process of converting information that is archived in DNA into molecules that actually do things in the cell occurs when proteingene product is synthesized and active 181 Gene Regulation and Information Flow most gene expression is triggered by specific signals from the environment 0 bacteria that live inon the body have to compete with each other for space and nutrients gt gt a cell has to use resources efficiently if it s going to survive and reproduce 0 an individual that synthesizes proteins it doesn t need has fewer resources to synthesize proteins it does need gt these cells compete less successfully Mechanisms of Regulation DNA gt mRNA gt protein gt activated protein gene expression can be controlled at any of these steps which means that a cell can avoid producing proteins that are not needed at the time by 1 avoid making mRNAs for a particular enzymes transcriptional control 0 saves the most energy for the cell 2 if the mRNA for an enzyme has been made the cell could prevent the mRNA from being translated into a protein translational control 0 allows cell to make rapid changes in the amount of different proteins because mRNA is already presentavailable for translation 3 many proteins have to be activated by chemical modification ie addition of a phosphate group posttranslational control 0 provides most rapid response these demonstrate tradeoff between the speed of the response and the conservation of resources 0 resources include ATP amino acids etc the ability to regulate gene expression allows cells to respond to changes in their environment 0 genes are not on or off their level of expression can be somewhere in between 182 Identifying Regulated Genes to find mutants that are associated with a particular trait two steps must be completed 1 generation of a large number of individuals with mutations at random locations on their genomes o mutagens things that cause cells to mutate gt Xrays UV rays chemicals that damage DNA 2 screen the treated individuals for mutants with defects in the process or biochemical pathway n question 183 Control of Transcription I two ways 1 negative control occurs when a regulatory protein called a repressor binds to DNA and shuts down transcription 2 positive control occurs when a regulatory protein called an activator binds to DNA and triggers transcription 185 Global Gene Regulation I gene expression is regulated by physical contact between regulatory proteins and specific regulatory sites in DNA I interactions among protein regulators and the DNA sequences they bind produce control over gene expression 0 gt regulation individual genes operons or large sets of genes Chapter 19 Control of Gene Expression in Eukaryotes I cells in a multicellular eukaryote express different genes in response to changes in the internal environment 0 specifically to signals from other cells I cells that are exposed to different cellcell signals express different genes 0 differential gene expression responsible for creating different cell types arranging them into tissues and coordinating their activity to form the multicellular society we call an individual 191 Gene Regulation in Eukaryotes I like bacteria eukaryotes can control gene expression at the levels of transcription translation and posttranslation o eukaryotes have three additional levels of control gt chromatin remodeling gt RNA processing gt mRNA life span 192 Chromatin Remodeling I for a molecular signal to trigger the transcription of a particular gene the chromatin around the target gene must be remodeled o chromatin structure in which DNA is wrapped around proteins I chromatin has several layers of organization 0 DNA complex is wrapped around histones to form nucleosomes gt histones DNAassociated proteins 0 nucleosomes are packed into 30nm fibers gt histones interact with one another and with the histones in other nucleosomes o 30nm fibers are attached to scaffold proteins gt now the entire chromosome is organized and held in place 0 entire assembly can be folded into the highly condensed structure needed for cell division I chromatin must be decondensed to expose the promoter so RNA polymerase can bind to it when genes are activated 0 DNA in condensed chromatin is protected from DNase gt DNase enzymes that cut DNA and can only work if DNA is in a decondensed configuration 0 when DNA is wrapped into a 30nm fiver the parking break is on gt gene expression depends on the chroatin being opened up in the promoter region I chromatin is altered by enzymes that add methyl groups to DNA that chemically modify histones and that reshape chromatin 0 DNA methylation occurs when a group of enzymes DNA methyltransferases to cytosine residues gt these sequences are recognized by proteins that trigger chromatin condensation o actively transcribed genes usually have low levels of CpG near their promoters nontranscribed genes usually have high levels 0 histone modification occurs when enzymes add chemical groups to specific amino acids of histone proteins gt addition of these groups promotes condensed or decondensed chromatin depending on the specific set of modification 0 acetylation of histones results in decondensed chromatin a state associated with active transcript o chromatin remodeling complexes are macromolecular machines that use ATP to reshape chromatin I DNA methylation and histone modification are examples of epigenetic inheritance 0 patterns of inheritance that are due to something other than differences in DNA sequences gt this is how cells within the body differ from each other 193 Initiating Transcription Regulatory Sequences and Proteins I the promoter is a site in DNA where RNA polymerase binds to initiate transcription 0 once a promoter that contains a TATA sequence has been exposed by chromatin remodeling the first step in initiating transcription is binding of the TATAbinding protein I promoterproximal elements are regulatory sequences near the promoter 0 these elements have sequences that are unique to specific sets of genes gt provide a mechanism for eukaryotic cells to express certain genes but not others I enhancers are regulatory sequences far downstream from the promoter 0 when regulatory proteins called transcriptional activators bind to enhancers transcription begins 0 when regulatory proteins called repressors bind to silencers transcription is shut down gt silencers DNA regulatory sequences that work to inhibit transcription 0 activators and repressors are regulatory proteins called transcription factors I differential gene expression is a result of the production or activation of specific transcription factors 0 genes are turned on when transcription factors bind to enhancers and promoter proximal elements 0 genes are turned off when transcription factors bind to silencers or when chromatin is condensed I differences in composition and shape of DNA bases exposed in the major and minor grooves of the double helix can be recognized by transcription factors I basal transcription factors are proteins that interact with the promoter and are not restricted to particular genes or cell types 0 TATAbinding protein I Mediator is a large complex of proteins that act as a bridge between regulatory transcription factors basal transcription factors and RNA polymerase I transcription is initiated in the following steps 1 chromatin remodeling o transcriptional activators recruit HATs and chromatin decondenses 2 exposure of promoter and regulatory sequences 0 region of DNA is exposed that includes the promoter promoterproximal element and other enhancers once chromatin decondenses 3 assembly of proteins 0 transcriptional activators bind to the newly exposed enhancers and promoter proximal element 0 basal transcription factors bind to the promoter and recruit RNA polymerase 4 DNA looping allows Mediator to connect DNAbound activators and basal transcription factors 0 formal beginning of transcription 194 PostTranscriptional Control A once a gene is transcribed a series of events which offer opportunity to regulate gene expression has to occur before a final product appears Alternative Splicing of mRNAs during splicing gene expression is regulated when selected exons are removed from the primary transcript along with the introns o the same primary RNA transcript can yield more than one kind of mature mRNA gt differ in the combinations of exons gt different proteins 0 referred to as alternative splicing alternative splicing is controlled by proteins that bind to RNAs in the nucleus and interact with spliceosomes to influence which sequences are used for splicing coding of proteins is determined by proteincoding genes regulatory sequences mRNA Stability and RNA Interference RNA interference occurs when a tiny singlestranded RNA held by a protein complex binds to a complementary sequence in an mRNA 0 results in the destruction of the mRNA or the blockage of translation 1 interference begins when RNA polymerase transcribes genes that code for RNAs that double back on themselves to form a hairpin 2 some of RNA is trimmed by enzymes in the nucleus and hairpin structure is exported to cytoplasm 3 in the cytoplasm another enzyme cuts out the hairpin loop to form doublestranded RNA molecules 4 one of the strands from this short RNA is taken up by a group of proteins called the M induced silencing complex RISC 0 RNA strand is hereby referred to as microRNA miRNA 5 miRNA binds to its complementary sequence in a target mRNA 6 if the match between the miRNA and the mRNA is good an enzyme in the RISC destroys the mRNA by cutting it in 2 o if match isn t perfect then mRNA is inhibited not destroyed Translation and PostTranslation Control I cells may slow down or stop translation in response to an increase in temperature or presence of virus 0 occurs due to phosphorylation addition of phosphate group to a protein by regulatory proteins I cells can keep an existing but inactive protein on hold and then quickly activate it in response to altered conditions 0 inefficient but speedy gt phosphorylation is a mechanism for activating or deactivating proteins I when a protein needs to be destroyed it is marked by enzymes with many copies of ubiquitin small polypeptide 0 this marking is recognized by proteasome and is cut into short segments 196 Linking Cancer with Defects in Gene Regulation I each type of cancer is caused by mutations that affect one of two classes of genes 0 genes that stopslow the cell cycle gt tumor suppressor genes are genes that code for proteins that stopslow the cell cycle when conditions are unfavorable for division 0 p53 is a tumor suppressor gene that is a regulatory transcription factor that serves as the master brake of the cell cycle 0 genes that trigger cell growthdivision by initiating specific phases in the cell cycle gt protooncogenes are genes that stimulate cell division 0 mutation converts protooncogenes to oncogenes allele that promotes cancer development
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