Chapter 15 Gene Regulation 2 Outline Prokaryotic Regulation

  • Slides: 35
Download presentation
Chapter 15 Gene Regulation

Chapter 15 Gene Regulation

2 Outline Prokaryotic Regulation trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control

2 Outline Prokaryotic Regulation 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

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

Repressible Operons: The trp Operon The regulator codes for a repressor If tryptophan (an

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 4

The trp Operon 5

The trp Operon 5

Inducible Operons: The lac Operon 6 The regulator codes for a repressor If lactose

Inducible Operons: The lac Operon 6 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 7

The lac Operon 7

Action of CAP 8

Action of CAP 8

9 Eukaryotic Regulation A variety of mechanisms Five primary levels of control: Nuclear levels

9 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 10

Regulation of Gene Expression: Levels of Control in Eukaryotes 10

11 Chromatin Structure Eukaryotic DNA associated with histone proteins Together make up chromatin As

11 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 12

Levels of Chromatin Structure 12

13 Chromatin Packing Euchromatin Loosely coiled DNA Transcriptionally active Heterochromatin Tightly packed DNA Transcriptionally

13 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

X-Inactivation in Mammalian Females 14

X-Inactivation in Mammalian Females 14

15 Transcriptional Control Transcription controlled by proteins called transcription factors Bind to enhancer DNA

15 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 16

Lampbrush Chromosomes 16

Initiation of Transcription 17

Initiation of Transcription 17

18 Posttranscriptional Control Posttranscriptional control operates on primary m. RNA transcript Given a specific

18 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 19

Processing of m. RNA Transcripts 19

20 Translational Control - Determines degree to which m. RNA is translated into a

20 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 21 Point Mutations Involve change in a single

Effect of Mutations on Protein Activity 21 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 22

Point Mutation 22

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

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

Androgen Insensitivity 24

Androgen Insensitivity 24

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

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

Error in Enzyme a 26

Error in Enzyme a 26

27 The gene that produces this enzyme is on chromosome 9

27 The gene that produces this enzyme is on chromosome 9

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

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

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

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

30 Carcinogenesis Development of cancer involves a series of mutations Proto-oncogenes – Stimulate cell

30 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 31

Carcinogenesis 31

Achondroplasia and Xeroderma Pigmentosum 32

Achondroplasia and Xeroderma Pigmentosum 32

33 Causes of Mutations Replication Errors 1 in 1, 000, 000 replications DNA polymerase

33 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

34 Review Prokaryotic Regulation trp Operon lac Operon Eukaryotic Regulation Transcriptional Control Posttranscriptional Control

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

Ending Slide Chapter 15 Gene Regulation

Ending Slide Chapter 15 Gene Regulation