Regulation ofGene Expression

Chapter 18

Warm Up

• Explain the difference between a missense and a nonsense mutation.

• What is a silent mutation?

QUIZ TOMORROW: Transcription/Translation. Write in your own words, what happens- describing initiation, elongation and termination in each!!!

Regulation of a Metabolic Pathway

A. Feedback Inhibition- inhibits the activity of the first enzyme in the metabolic pathway.

A. Regulation of Gene Expression- enzymes are controlled at the transcription level, by turning genes on/off.

Operons

• Operator- a segment of DNA that controls the access of RNA polymerase to the genes. Found within the promoter sequence. (on/off switch)

• Operon- the operator, promoter, and genes they control- the entire stretch of DNA required for metabolic pathway. (trp operon)

Types of Operons

• Repressible Operon- usually on but can be inhibited. (Ex: trp operon)

• Inducible Operon- usually off but can be stimulated. (Ex: lac operon)

*Both are examples of negative gene regulation.

Repressible Operons

• Repressor- protein that can turn off the operon by binding to the operator and blocking the attachment of RNA polymerase, preventing transcription of the genes.

• Regulatory Gene- codes for a repressor or similar protein that controls the transcription of another gene or group of genes.

• Corepressor- a small molecule that cooperates with a repressor protein to switch an operon off.

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Inducible Operons

• Inducer- a small specific molecule that binds to the repressor which inactivates it.

Positive Gene Regulation

• Activator- a protein that binds to DNA and stimulates transcription of a gene.

Exit Slip

• A certain mutation in E.coli changes the lac operator so that the active repressor cannot bind. How would this affect the cells production of B-galactosidase?

Warm Up Exercise

• Explain the difference in an inducer and a repressor operon.

Gene Expression

• Differential Gene Expression- the expression of different genes by cells with the same genome.

• Gene expression typically refers to actions occurring in transcription, but regulation can happen at other stages in more complex organisms.

Chromosomal Modification

• Epigenetic Inheritance- inheritance of traits transmitted by mechanisms not directly involving the nucleotide sequence.– Ex: histone acetylation and DNA methylation

Chromosomal Modification

• Histone Acetylation- acetyl groups are attached to lysines in histone tails. – Neutralizes the positive charge on the lysine which

cause histones to not bind to neighboring nucleosomes. Causes chromatin to form a looser structure.

• Deacetylation- removal of acetyl groups.

Chromosomal Modification

• DNA Methylation- methyl groups are attached to bases in the DNA (usually cytosine).– Inactive DNA is typically more methylated than

regions that are actively transcribed. Individual genes are usually more methylated in cells where they are not expressed.

Regulation of Transcription Initiation

• Control Elements- segments of noncoding DNA that serve as binding sites for transcription factors (proteins that regulate transcription).– Proximal Control Elements (near promoter) vs.

Distal Control Elements called Enhancers (upstream or downstream of a gene or within an intron)

Transcription

INSERT FIGURE 18.10

Coordinate Control in Eukaryotes

• Genes with the same control elements are activated by the same chemical signals. (Not by a common operator, as in prokaryotes).

Warm Up Exercise

• Explain how DNA methylation and histone acetylation affect transcription of genes.

Post-Transcriptional Regulation

• Alternative RNA Splicing- different mRNA molecules are produced from the same primary transcript, depending on which segments are treated as introns or exons.

Post Transcriptional Regulation

• mRNA Degradation- nucleotide sequences (in UTR) determine how long mRNA remains intact. By degrading mRNA, expression is blocked.

• Initiation of Translation- by preventing the attachment of mRNA on ribosomes, translation is blocked. – Can occur when regulatory proteins bind to

sequences in UTR, when poly-A tail isn’t sufficient in length, or when translation initiation factors are deactivated.

Post-Transcriptional Regulation

• Chemical modifications to polypeptides to make them functional.

• Transport to target destinations.• Length of time for protein to function in the cell.

– When cells are marked for destruction, a protein called ubiquitin is attached to the protein surface.

– Proteosomes- complexes that recognize ubiquitin and degrade marked proteins.

Noncoding RNA- Sec. 18.3

• Protein coding DNA = 1.5% of human genome. Very small percent of non-coding DNA codes for genes of rRNA/tRNA. Significant amount of genome may be transcribed into noncoding RNA (ncRNA)

Noncoding RNA

• MicroRNA (miRNA)- bind to complementary mRNA and degrades or prevents translation.

Noncoding RNA

• RNA Interference- injecting double-stranded RNA molecules into a cell turns off expression of a gene with the same sequence as the RNA.

• Small Interfering RNA (siRNA)-

Warm Up Exercise

• Draw a diagram that represents how Alternative RNA Splicing can code for two different proteins.

• How is a protein targeted for degradation, and what cellular component is responsible for degrading it?

Genetic Programming for Embryonic Development- Sec. 4

• Cell Division- zygote gives rise to a large number or identical cells.

• Cell Differentiation- become specialized in structure and function and organize into tissues and organs.

• Morphogenesis- “creation of form”

Differential Gene Expression

• Cytoplasmic Determinants- maternal substances in the egg that influence the course of development. (non-homogenous)

Differential Gene Expression

• Inductive Signals- signals from other nearby embryonic cells that cause a change in gene expression- sending a cell down a specific developmental path.

Differential Gene Expression

• Determination- events that lead to the observable differentiation of a cell.

Pattern Formation

• Homeotic Genes- determine pattern formation.– Embryonic Lethals- mutations with phenotypes

causing death at the embryonic stage.

• Maternal Effect Gene- when mutant in mother, results in mutant phenotype in offspring, regardless of offspring’s own genotype.

• Morphogens- establish an embryo’s axis and other features of its form.

Warm Up Exercise

• Explain the effect of cytoplasmic determinants on cells and cell differentiation.

• Describe what is meant by the term “embryonic lethals”?

Cancer Control

• p53 Gene- codes for a transcription factor that promotes synthesis of cell-cycle inhibiting proteins.– Mutation is this gene usually leads to excessive cell

growth and cancer.