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Regulation of Gene Expression Step 1 of Transcription What is “Gene Expression”? Some proteins are always necessary for an organism’s survival and continuously produced: Expression of the – RNA/DNA Polymerase gene is always – Glycoproteins occurring Other proteins need to be produced at certain times and in certain amounts. Expression of the gene is turned “on” or “off” Why would a cell want to turn off a gene? All cells carry the same genetic information, but each type of cell expresses only a fraction of its genes (cellular differentiation). Insects change through a variety of body shapes during their life cycle which can be accounted for by changing gene expression. Expression of different genes at different times also accounts for the different stages vertebrate embryos go through as they develop. ***Control of gene expression is complex, interrelated and much is still being discovered*** Mechanisms of regulating gene expression: Epigenics Proteins Environment Nucleosomes Regulation of Gene Expression by Proteins Recall with your partner: what a promoter is and what it does. Regulation of Gene Expression by Proteins • A promoter is a sequence of base pairs located near a gene that onto which RNA polymerase binds. • It does not code for a protein but plays a role in protein synthesis by initiating transcription. Regulation of Gene Expression by Proteins Proteins can attach to the DNA near the promoter to make the DNA more or less accessible for RNA polymerase PROTEINS DNA Transcription factors AKA Activators Enhancer (increase gene expression) (increase gene expression) Repressor proteins Silencer (decrease gene expression) (decrease gene expression) Regulation of Gene Expression by Proteins For example: E.coli has genes to produce the enzyme necessary to digest the sugar lactose- but it only activates them in the presence of lactose. (WHY?) An operator is a sequence next to the promoter. Transcription factors can bind to it and turn on gene expression. Regulation of Gene Expression by Proteins Repressor proteins are normally produced and will bind to the operator preventing transcription for the lactase gene. If lactose if present, it will bind to the repressor protein which will change its shape and prevent it from binding on the operator. This is known as the lac operon in prokaryotes. Operon refers to a cluster of genes under the control of a single promoter. Enhancers Sequence on the DNA that increase the rate of transcription when proteins bind to them. Silencers Sequence on the DNA that decreases the rate of transcription when proteins bind to them. Mechanisms of regulating gene expression: Epigenics Proteins Environment Nucleosomes Nucleosomes Regulate Transcription Eukaryotic DNA is associated with proteins called histones. The DNA is wrapped around a core of 8 histone molecules which is known as a nucleosome. Nucleosomes are then compacted in chromatin fibers. BIG IDEA: chemical modification of histone tails through acetyl/methyl groups can either activate or deactivate genes by decreasing or increasing the accessibility of genes to transcription factors. acetyl group Nucleosomes Regulate Transcription “Chemical tag” Acetylation is the adding of an acetyl group Methylation is the adding of a methyl group Nucleosomes Regulate Transcription Histone acetylation allows a less condensed DNA with higher levels of transcription. Non-acetylated histones form a tightly bound structure that inhibits transcription of the genes there. Nucleosomes Regulate Transcription DNA methylation typically turns off genes (through a mechanism that isn’t well understood yet). Mechanisms of regulating gene expression: Epigenics Proteins Environment Nucleosomes Reading at: https://www.genome.gov/27532724 1. What is the epigenome? 2. What does it do? 3. What makes it up? 4. Can it change? There is substantial evidence that smoking increases the rate of DNA methylation. Mothers who smoke while pregnant have been shown to influence the methylation patterns of their unborn children too! • What does DNA methylation do? • What if a tumor suppressor gene is methylated? Epigenetics Extra Credit Opportunity: There is even mounting evidence that the chemical modifications that occur to the DNA in gametes could in certain circumstances be passed on to the next generation both at the cellular as well as whole organism level. Mechanisms of regulating gene expression: Epigenic tags Proteins Environment Nucleosomes Regulation of Gene Expression by the Environment Example #6 of regulating gene expression: UV exposure increases expression of the gene that codes for the melanin protein. Regulation of Gene Expression by the Environment Regulation of Gene Expression by the Environment For some traits, it can be hard to tell how much influence the environment has over gene expression. Comparing identical to fraternal twins can be helpful in determining this. Why do you think this is? Think: Determine the percentage of identical twins where both have diabetes. Explain why a higher % of identical twins sharing a trait suggests that a genetic component contributes to the onset of the trait.