Regulation of Gene 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.

B.  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.

•  kl

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.

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. •  Tumor-Suppressor Genes- code for proteins

that help prevent uncontrolled cell growth.