Chapter 15 Gene Regulation Gene Regulation Outline Prokaryotic

Chapter 15 Gene Regulation

Gene Regulation Outline Prokaryotic Regulation trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control Genetic Mutations Cancer 2

Gene Regulation 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 Short segment of DNA Structural Genes One to several genes coding for enzymes of a metabolic pathway Translated simultaneously as a block Long segment of DNA 3

Inducible Operons: The lac Operon Gene Regulation 4 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 5

Repressible Operons: The trp Operon 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 6

The trp Operon 7

Gene Regulation Eukaryotic Regulation. OMIT MOST FOR MAGNET! A variety of mechanisms Five primary levels of control: Nuclear levels Chromatin Packing- KNOW Transcriptional Control- KNOW intron vs exon Posttranscriptional Control- OMIT Cytoplasmic levels Translational Control-OMIT Posttranslational Control- OMIT 8

Regulation of Gene Expression: Levels of Control in Eukaryotes- Most not emphasized Mag Bio. Do chromatin packing & introns/exons 9

Gene Regulation 10 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 11

Gene Regulation Chromatin Packing Euchromatin 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 12

X-Inactivation in Mammalian Females 13

Gene Regulation 14 Transcriptional Control- omit Mag Bio 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

Initiation of Transcription- Omit Magnet Bio 15

Gene Regulation 16 Posttranscriptional Control Posttranscriptional control operates on primary m. RNA 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 m. RNA 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 m. RNA Transcripts- omit Mag Bio 17

Gene Regulation 18 Translational Control- omit Mag Bio Translational Control - Determines degree to which m. RNA 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 Gene Regulation 19 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 : After deletion: After insertion: THE CAT ATE THE RAT THE ATA TET HER AT THE CCA TAT ETH ERA T

Point Mutation 20

Gene Regulation 21 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 22

Gene Regulation Causes of Mutations Replication Errors 1 in 1, 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 23

Gene Regulation Review Prokaryotic Regulation trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control Genetic Mutations Cancer 24