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Gene RegulationControl Mechanisms

Gene Regulation~ 42,000 genes exist that code for proteins in humansNot all proteins are required all the timeExample: Insulin only required when glucose level is highGene Regulation is a mechanism turning on or off of specific genes depending on the requirements of the organism Gene regulation is vital to an organisms survival

Housekeeping GenesGenes that are switched on all the time because they are always needed in the cell for life functionsThese genes are constantly transcribed and translated

Transcription FactorsProteins that switch on genes by binding to DNA and helping the RNA polymerase to bind

Turn on genes when required

In Eukaryotic CellsFour Leves of Control of Gene Expression

The mRNA molecules undergo changes in the nucleus before translation occursIntrons are removed and exons are spliced togetherTwo important regulatory mechanisms:OperonsCluster of genes, often functionally related, forming a tight cluster on the genomePrimarily occurring in prokaryotes (such as bacteria)Also some in eukaryotesControlled by a common ON/OFF switchOperons are under the control of regulatory elements and factors that bind to these elements. What are these elements?

OperonsOperonsTranscription of the cluster results in a single molecule, The molecule is a multi-gene transcript of mRNAIt codes for several proteins and is directly translated into distinct protein products.

Operon Gene RegulationControl of an operon is a type of gene regulation that enables organisms to regulate the expression of various genes depending on environmental conditions.

Operon regulation can be either negative or positive by induction or repression.

Operon Gene RegulationOperon Gene RegulationInduction and repression respond to specific substances, called effectorsEffectors control the activity of a specific set of genesThe lac OperonThe lac operon is a cluster of genes of the model bacterium Escherichia coli The first operon to be discovered The lac operon is regulated by several factors including the availability of glucose and lactose. It consists of a promoter, an operator, followed by a group of lactose-utilizing genes Promoter: the binding site of RNA polymerase.Operator: regulatory sequence that act as switch.

LactoseA disaccharide found in milk or milk productsConsists of two sugars: glucose and galactoseE coli found on the intestinal lining of mammals can use the energy supplied by lactose for growthTo use the energy, E coli must split lactose into its two monomer sugars

GlucoseGalactoseEscherichia coliE coli produces an enzyme to degrade lactoseEnzyme called -galactosidaseThere is no need for E coli to produce this enzyme at all timesIt only produces the enzyme when lactose is presentE coli uses negative regulation to control the transcription and translation of the -galactosidase gene

Negative control systemThe lac OperonThe lactose-utilizing genes are:lac Z, lac Y, and lac Alac Z gene encodes the enzyme -galactosidaselac Y gene encodes -galactosidase permease (an enzyme that causes lactose to permeate the cell membrane and enter the cell)lac A gene encodes a transacetylase (function unknown)

lac Zlac Ylac ALacl Protein: A repressor proteinBlocks the transcription of the -galactosidase gene It does that by binding to the Lactose operator and getting in the way of the RNA polymerase

(Repressor protein: regulatory molecule binding to an operator site and preventing transcription of an operon)When lactose is not presentThe promoter and operator regions overlapWhen the Lacl protein binds to the operator, it converts part of the promoter, which is the binding site for RNA polymerase

When lactose is presentThe presence of lactose removes Lacl protein (repressor)Therefore, lactose is known as the signal molecule or an inducer

Protein TranscriptionLactose binds to the Lacl protein changing the conformation of the Lacl proteinThis change results in the inability of the new complex to stay bound to the operator region of the lac operonThe complex falls off the DNA allowing RNA polymerase to proceed onward and transcribe the lac operon

In the case of the lac Operon, the level of lactose is an effector, meaning that it controlsthe activity of a specific set of genes

The lac Operon is an example of enzymeinduction

Operon Gene RegulationThe trp OperonAnother example of coordinated regulationIn contrast to the lac Operon (transcription induced with presence of lactose), the trp Operon is repressed when high levels of tryptophan are present.In this case, the effector is the level of tryptophanTryptophan is an amino acid that is used by E coli cells for the production of proteinE coli cells located on the intestinal lining of a mammal can absorb tryptophan from the mammals dietThe trp OperonConsists of five genesThese five genes code for five polypeptides that make three enzymes needed to synthesize tryptophan

CorepressorSince tryptophan itself is needed to inactivate the trp operon, it is called a corepressorCorepressor: - a molecule that binds to a repressor to activate it- usually the product of an operon

When Tryptophan Level is lowWhen the level of tryptophan is low, the shape of the trp pressor protein changes This is due to the lack of tryptophan corepressorThe trp repressor can no longer stay bound to the trp operator and it falls offThe RNA polymerase is free to transcribe the trp operon genesThis results in an increase in tryptophan production

When Tryptophan Level is highThe amino acid tryptophan binds to the trp repressor protein, altering its shapeThe trp-repressor-tryptophan complex can now bind to the trp operatorThis way transcription is blocked

lac OperonThe lacl repressor protein binds to the operator when lactose levels are lowHigh level of lactose induce the operontrp OperonThe corepressor tryptophan binds to the trp repressor protein, and the complex binds to the operator when tryptophan levels are highHigh levels of tryptophan repress the operon

Comparison of the lac Operon and the trp OperonComparison of the lac Operon and the trp OperonComparison of the lac Operon and the trp OperonComparison of the lac Operon and the trp OperonComparison of the lac Operon and the trp Operon

lac Operon trp Operon