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
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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
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The trp Operon
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Inducible Operons:
The lac Operon
Gene Regulation
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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
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Action of CAP
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Gene Regulation
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
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Regulation of Gene Expression:
Levels of Control in Eukaryotes
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Gene Regulation
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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
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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
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X-Inactivation in Mammalian Females 14
Gene Regulation
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
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Initiation of Transcription
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Gene Regulation
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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
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Gene Regulation
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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
Gene Regulation
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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
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Faulty Proteins = Genetic Disorders
Examples:
Sickle cell anemia
Hemophilia
PKU
Albinism
Huntington’s Disease
Androgen insensitivity
Androgen Insensitivity
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Ea
A
(phe)
B
(tyr)
Eb
C
(Melanin)
Error in Enzyme a
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27
The gene
that
produces
this
enzyme
is on
chromosome 9
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The blood in the retina and iris
reflects red light, resulting in pink
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Gene Regulation
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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
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Achondroplasia and
Xeroderma Pigmentosum
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Gene Regulation
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
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Gene Regulation
Review
Prokaryotic Regulation
trp Operon
lac Operon
Eukaryotic Regulation
Transcriptional Control
Posttranscriptional Control
Translational Control
Posttranslational Control
Genetic Mutations
Cancer
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Ending Slide Chapter 15
Gene Regulation