Biology, 9th ed,Sylvia Mader Chapter 15 Chapter 15 Gene Regulation Gene Regulation

Outline Prokaryotic Regulation Eukaryotic Regulation Genetic Mutations trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control Genetic Mutations Cancer

Prokaryotic Regulation: The Operon Model Operon consist of three components Promoter DNA sequence where RNA polymerase first attaches Short segment of DNA Operator DNA sequence where active repressor binds Structural Genes One to several genes coding for enzymes of a metabolic pathway Translated simultaneously as a block Long segment of DNA

Repressible Operons: The trp Operon The regulator codes for a repressor If tryptophan (an amino acid) is absent: Repressor is unable to attach to the operator (expression is normally “on”) RNA polymerase binds to the promoter Enzymes for synthesis of tryptophan are produced If tryptophan is present: Combines with repressor as corepressor Repressor becomes functional Blocks synthesis of enzymes and tryptophan

The trp Operon

Inducible Operons: The lac Operon The regulator codes for a repressor If lactose (a sugar that can be used for food) is absent: Repressor attaches to the operator Expression is normally “off” If lactose is present: It combines with repressor and renders it unable to bind to operator RNA polymerase binds to the promoter The three enzymes necessary for lactose catabolism are produced

The lac Operon

Action of CAP

Eukaryotic Regulation A variety of mechanisms Five primary levels of control: Nuclear levels Chromatin Packing Transcriptional Control Posttranscriptional Control Cytoplasmic levels Translational Control Posttranslational Control

Regulation of Gene Expression: Levels of Control in Eukaryotes

Eukaryotic DNA associated with histone proteins Chromatin Structure Eukaryotic DNA associated with histone proteins Together make up chromatin As seen in the interphase nucleus Nucleosomes: DNA wound around balls of eight molecules of histone proteins Looks like beads on a string Each bead a nucleosome The levels of chromatin packing determined by degree of nucleosome coiling

Levels of Chromatin Structure

Chromatin Packing Euchromatin Heterochromatin Barr Bodies Loosely coiled DNA Transcriptionally active Heterochromatin Tightly packed DNA Transcriptionally inactive Barr Bodies Females have two X chromosomes, but only one is active Other is tightly packed along its entire length Inactive X chromosome is Barr body

X-Inactivation in Mammalian Females

Transcriptional Control Transcription controlled by proteins called transcription factors Bind to enhancer DNA Regions of DNA where factors that regulate transcription can also bind Always present in cell, but most likely have to be activated before they will bind to DNA

Lampbrush Chromosomes

Initiation of Transcription

Posttranscriptional Control Posttranscriptional control operates on primary mRNA transcript Given a specific primary transcript: Excision of introns can vary Splicing of exons can vary Determines the type of mature transcript that leaves the nucleus May also control speed of mRNA transport from nucleus to cytoplasm Will affect the number of transcripts arriving at rough ER And therefore the amount of gene product realized per unit time

Processing of mRNA Transcripts

Translational Control Translational Control - Determines degree to which mRNA is translated into a protein product Presence of 5′ cap Length of poly-A tail on 3′ end Posttranslational Control - Affects the activity of a protein product Activation Degradation rate

Effect of Mutations on Protein Activity Point Mutations Involve change in a single DNA nucleotide Changes one codon to a different codon Affects on protein vary: Nonfunctional Reduced functionality Unaffected Frameshift Mutations One or two nucleotides are either inserted or deleted from DNA Protein always rendered nonfunctional Normal : THE CAT ATE THE RAT After deletion: THE ATA TET HER AT After insertion: THE CCA TAT ETH ERA T

Point Mutation

Faulty Proteins = Genetic Disorders Examples: Sickle cell anemia Hemophilia PKU Albinism Huntington’s Disease Androgen insensitivity

Androgen Insensitivity

Ea Eb A B C (phe) (tyr) (Melanin)

Error in Enzyme a

The gene that produces this enzyme is on chromo-some 9

The blood in the retina and iris reflects red light, resulting in pink eyes.

We will revisit this section after Mendelian Genetics! TEST ON WED! Ch 14 and Ch 15

Development of cancer involves a series of mutations Carcinogenesis Development of cancer involves a series of mutations Proto-oncogenes – Stimulate cell cycle Tumor suppressor genes – inhibit cell cycle Mutation in oncogene and tumor suppressor gene: Stimulates cell cycle uncontrollably Leads to tumor formation

Carcinogenesis

Achondroplasia and Xeroderma Pigmentosum

Environmental Mutagens Causes of Mutations Replication Errors 1 in 1,000,000,000 replications DNA polymerase Proofreads new strands Generally corrects errors Environmental Mutagens Carcinogens - Mutagens that increase the chances of cancer Ultraviolet Radiation Tobacco Smoke

Review Prokaryotic Regulation Eukaryotic Regulation Genetic Mutations trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control Genetic Mutations Cancer

Biology, 9th ed,Sylvia Mader Chapter 15 Ending Slide Chapter 15 Gene Regulation Gene Regulation