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Chapter 18. Regulation of Gene Expression. Regulation of Gene Expression. Important for cellular control and differentiation. Understanding “expression” is a “hot” area in Biology. General Mechanisms. 1. Regulate Gene Expression 2. Regulate Protein Activity. Operon Model.
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Chapter 18 Regulation of Gene Expression
Regulation of Gene Expression • Important for cellular control and differentiation. • Understanding “expression” is a “hot” area in Biology.
General Mechanisms 1. Regulate Gene Expression 2. Regulate Protein Activity
Operon Model • Jacob and Monod (1961) - Prokaryotic model of gene control. • Always on the National AP Biology exam !
Operon Structure 1. Regulatory Gene 2. Operon Area a. Promoter b. Operator c. Structural Genes
Regulatory Gene • Makes Repressor Protein which may bind to the operator. • Repressor protein blocks transcription.
Promoter • Attachment sequence on the DNA for RNA polymerase to start transcription.
Operator • The "Switch”, binding site for Repressor Protein. • If blocked, will not permit RNA polymerase to pass, preventing transcription.
Structural Genes • Make the enzymes for the metabolic pathway.
Lac Operon • For digesting Lactose. • Inducible Operon - only works (on) when the substrate (lactose) is present.
If no Lactose • Repressor binds to operator. • Operon is "off”, no transcription, no enzymes made
If Lactose is present • Repressor binds to Lactose instead of operator. • Operon is "on”, transcription occurs, enzymes are made.
Enzymes • Digest Lactose. • When enough Lactose is digested, the Repressor can bind to the operator and switch the Operon "off”.
Net Result • The cell only makes the Lactose digestive enzymes when the substrate is present, saving time and energy.
Animation • http://www.biostudio.com/d_%20Lac%20Operon.htm
trp Operon • Makes Tryptophan. • Repressible Operon.
If no Tryptophan • Repressor protein is inactive, Operon "on” Tryptophan made. • “Normal” state for the cell.
If Tryptophan present • Repressor protein is active, Operon "off”, no transcription, no enzymes. • Result - no Tryptophan made.
Repressible Operons • Are examples of Feedback Inhibition. • Result - keeps the substrate at a constant level.
Eukaryotic Gene Regulation • Can occur at any stage between DNA and Protein. • Be prepared to talk about several mechanisms in some detail.
Chromatin Structure • Histone Modifications • DNA Methylation • Epigenetic Inheritance
Histone Acetylation • Attachment of acetyl groups (-COCH3) to AAs in histones. • Result - DNA held less tightly to the nucleosomes, more accessible for transcription.
DNA Methylation • Addition of methyl groups (-CH3) to DNA bases. • Result - long-term shut-down of DNA transcription. • Ex: Barr bodies, genomic imprinting
Epigenetics • Another example of DNA methylation effecting the control of gene expression. • Long term control from generation to generation. • Tends to turn genes “off”.
Do Identical Twins have Identical DNA? • Yes – at the early stages of their lives. • Later – methylation patterns change their DNA and they become less alike with age.
Transcriptional Control • Enhancers and Repressors • Specific Transcription Factors • Result – affect the transcription of DNA into mRNA
Enhancers • Areas of DNA that increase transcription. • May be widely separated from the gene (usually upstream).
Posttranscriptional Control • Alternative RNA Processing Ex - introns and exons • Can have choices on which exons to keep and which to discard. • Result – different mRNA and different proteins.
Results • Bcl-XL – inhibits apoptosis • Bcl-XS – induces apoptosis • Two different and opposite effects!!
Commentary • Alternative Splicing is going to be a BIG topic in Biology. • About 60% of genes are estimated to have alternative splicing sites. (way to increase the number of our genes) • One “gene” does not equal one polypeptide (or RNA).
Other post transcriptional control points • RNA Transport - moving the mRNA into the cytoplasm. • RNA Degradation - breaking down old mRNA.
Translation Control • Regulated by the availability of initiation factors. • Availability of tRNAs, AAs and other protein synthesis factors. (review Chapter 17).
Protein Processing and Degradation • Changes to the protein structure after translation. • Ex: Cleavage • Modifications • Activation • Transport • Degradation
Protein Degradation • By Proteosomes using Ubiquitin to mark the protein.
Noncoding RNA • Small RNA molecules that are not translated into protein. • Whole new area in gene regulation. • Ex - RNAi
Types of RNA • MicroRNAs or miRNAs. • RNA Interference or RNAi using small interfering RNAs or siRNAs. • Both made from RNA molecule that is diced into double stranded (ds) segments.
RNAi • siRNAs or miRNAs can interact with mRNA and destroy the mRNA or block translation. • A high percentage of our DNA produces regulatory RNA.