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

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

3. 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

4. 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

5. The trp Operon

6. 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

7. The lac Operon

8. Action of CAP

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

10. Regulation of Gene Expression: Levels of Control in Eukaryotes

11. 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

12. Levels of Chromatin Structure

13. 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

14. X-Inactivation in Mammalian Females

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

16. Lampbrush Chromosomes

17. Initiation of Transcription

18. 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

19. Processing of mRNA Transcripts

20. 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

21. 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

22. Point Mutation

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

24. Androgen Insensitivity

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

26. Error in Enzyme a

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

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

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

30. 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

31. Carcinogenesis

32. Achondroplasia and Xeroderma Pigmentosum

33. 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

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

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