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 Biology, 9th ed,Sylvia Mader Prokaryotic Regulation: The Operon Model Chapter 15 Gene Regulation 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 2.C.1: Operons in gene regulation 3.B.1: Promoters

Repressible Operons: The trp Operon Biology, 9th ed,Sylvia Mader Repressible Operons: The trp Operon Chapter 15 Gene Regulation 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

Inducible Operons: The lac Operon Biology, 9th ed,Sylvia Mader Inducible Operons: The lac Operon Chapter 15 Gene Regulation 4.C.2: Effect of adding lactose to a Lac + bacterial culture 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

Biology, 9th ed,Sylvia Mader Chapter 15 Action of CAP Gene Regulation 3.B.2: Levels of cAMP regulate metabolic gene expression in bacteria.

Eukaryotic Regulation Biology, 9th ed,Sylvia Mader Eukaryotic Regulation Chapter 15 Gene 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 Biology, 9th ed,Sylvia Mader Regulation of Gene Expression: Levels of Control in Eukaryotes Chapter 15 Gene Regulation 3.B.1: Promoters 3.B.1: Enhancers

Levels of Chromatin Structure Biology, 9th ed,Sylvia Mader Levels of Chromatin Structure Chapter 15 Gene Regulation 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

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 Biology, 9th ed,Sylvia Mader Transcriptional Control Chapter 15 Gene Regulation 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 3.C.3: Transposons present in incoming DNA (transposons are specific DNA sequences that have the remarkable ability to move within and between chromosomes; sometimes act like regulator genes because movement to new locations sometimes alters neighboring genes, decreasing their expression)

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 Biology, 9th ed,Sylvia Mader Effect of Mutations on Protein Activity Chapter 15 Gene Regulation 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 3.D.1: DNA repair mechanisms (DNA repair enzymes constantly monitor DNA and fix irregularities)

Point Mutation

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

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