Gene Regulation

Lac Operon

Eukaryotes use four primary ways to control the expression of genes.

• Transcriptional control – selection of genes to be transcribed and the rate of

transcription • Posttranscriptional control

– processing of mRNA and the rate at which mRNA leaves the nucleus.

• Translational control – how long mRNA remains in the cytoplasm

• Posttranslational control – additional processing that proteins require to be

functional or through feedback inhibition.

Oncogenes

• Genes that are responsible for signaling cells to divide - called proto-oncogenes

• When damaged cause uncontrolled cell division

• Carcinogen– Agents that cause cancer

(mutations)– include radiation, cigarette

smoke, and viruses

Normal Cells:Controlled growthContact inhibitionOne organized layerDifferentiated cells

Cancer Cells:Uncontrolled growthNo contact inhibitionDisorganized, multilayeredNondifferentiated cellsAbnormal nuclei

Mutagens• Spontaneous

– Alkylation– Oxidation– Etc

• Radiation– UV– Gamma, Beta, Alpha– Etc

• Chemical– Base analogue– Intercalating agents– Etc

Mutations

Gene Regulation in Prokaryotes

• In prokaryotes, genes must also be turned on and off.

• If genes are always expressed, then much energy is wasted. The organism will quickly become lethargic and very tired.

• An Operon consists of:– structural genes– promoter – Operator– Regulatory genes– Repressor and activator proteins

Repressible Operon - trp• repressible operon is ON by default. • regulatory genes produce inactive repressors. • end product of the pathway, tryptophan, interacts with the

inactive repressor (acting as a co-repressor), and causes a conformational change in the repressor.

• The active repressor is now able to bond to the operator and switch off transcription.

• Typical of anabolic pathways• http://bcs.whfreeman.com/thelifewire/content/chp13/13020

02.html• http://www.as.wvu.edu/~dray/219files/TrpAttenuation.mov

Inducible Operon - lac

Negative Regulation• Regulatory gene produces repressor• Repressor is bound to the Operator• Allolactose will bond to repressor protein• Repressor will be removed Operator• RNA polymerase can transcribe• http://bcs.whfreeman.com/thelifewire/content/chp

13/1302001.html• http://www.as.wvu.edu/~dray/219files/LacOperon.

mov

Lactose metabolism in E. coli

1. Transport lactose into the cell2. Break down lactose into glucose and

galactose

galactose glucose

lactoseGalactoside permease

E. Coli cell

Lactose metabolism in E. coli

• The enzyme Beta-galactosidase breaks down lactose into glucose and galactose

+Beta-galactosidase

Lac Operon Genes

• Operon: a group of genes that are commonly regulated and transcribed into mRNA

Name of the Gene Protein Product of the Gene

Lac I Gene Produces a Repressor Protein

Lac Z Gene Produces Beta-Galactosidase

Lac Y Gene Produces Galactoside Permease

Lac A Gene Produces Transacetylase

Role of lactose

• Lactose is called an inducer molecule because it signals the production of:

(a)Beta-galactosidase: the enzyme that cleaves lactose into glucose and galactose

(b)Galactoside permease: the transport protein that allows lactose to enter a cell

(c)Transacetylase: don’t worry about this one