CHAPTER 15
Gene Regulation
REGULATION OF GENE ACTIVITY
1
Outline
Prokaryotic Regulation
trp Operon
lac Operon
Eukaryotic Regulation
Transcriptional Control
Posttranscriptional Control
Translational Control
Posttranslational Control
Genetic Mutations
Cancer
Gene Regulation
2
Gene Regulation
Pg 252
Structural
Genes
Operon
consist
of three components
Operator
-Onesequence
to several where
genes coding
enzymes of a
Promoter
-DNA
activefor
repressor
metabolic
pathway
-DNA sequence
where RNA polymerase first
binds
-Translated
simultaneously as a block
attaches
-Short segment of DNA
-Long
-Short segment
segment of
of DNA
DNA
3
The trp 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
Gene Regulation
trp Operon Animations
 Animation #1
 Animation #2
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The lac Operon
8
Inducible Operons:
The lac Operon
Gene Regulation
9
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
10
Action of CAP
Gene Regulation
11
Lac Operon Animations
 Animation #1
 Lac Operon Induction
& Quiz
Gene Regulation
12
Negative vs Positive Control
1. Negative Control - Active
repressors shut down activity of
an operon
2. Positive Control - when CAP
molecule is active, it promotes
activity of operon.
 Use of both positive and negative
controls allows cell to fine-tune its
control of metabolism.
Regulation of Gene14
Expression:
Levels of Control in
Eukaryotes
Five primary levels of control:
Nuclear levels
-Chromatin Packing
-Transcriptional Control
-Posttranscriptional
Control
Cytoplasmic levels
-Translational Control
-Posttranslational Control
Levels of Chromatin Structure
16
Eukaryotic DNA associated
with histone proteins
Together make up
chromatin
As seen in the interphase
nucleus
Figure 15.5c
Nucleosomes:
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The
levels
of chromatin
DNA
wound around
balls of eightpacking
molecules of
histone proteins
determined
by degree of nucleosome
Looks like beads on a string
coiling
Each bead a nucleosome
Gene Regulation
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Chromatin Packing
Euchromatin
Loosely coiled DNA
Transcriptionally active
Heterochromatin
Tightly packed DNA
Transcriptionally inactive
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X-Inactivation in Mammalian Females
Barr Bodies - Animation
Females have two X chromosomes, but only one is
active
Other is tightly packed along its entire length
Inactive X chromosome is Barr body
Initiation of
Transcription
Transcription
Bind to
Always
controlled
by
enhancer
present
inDNA
cell,proteins
but most
Regions
ofto
called
likely
have
DNA
where
transcription
be
activated
factors
that
factors
before
they
regulate
will
bind
to
transcription
DNA
can also bind
20
Lampbrush
Chromosomes
These
Each
chromosomes has
are
chromosome
present
inloops
maturing
many
amphibian
egg
cells
extended from its
and
give
evidence
axis
(white).
Many
that when mRNA is
mRNA
transcripts
being synthesized,
are being made
chromosomes
most
off these
DNA
likely
decondense.
loops (red)
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Processing of
mRNA
Transcripts
Control speed of
Excision
of
mRNA transport
introns
can vary
from nucleus
to
cytoplasm
Splicing of
Will
affect
exons
canthe
vary
number of
Determines
the
transcripts arriving
type
of mature
at rough
ER
transcript
thatthe
And therefore
leaves
amount the
of gene
nucleus
product realized
per unit time
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Gene Regulation
25
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
Gene Regulation
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Post-Translational Control
•Posttranslational Control begins
once a protein has been
synthesized
Some Proteins are not immediately
active after synthesis.
-Cleaving and recombining
Some proteins are short-lived
-Degraded and Destroyed
(Proteasomes)
Effect of Mutations on
Protein Activity
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
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Effect of Mutations on
Protein Activity
Gene Regulation
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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
Point Mutation
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Androgen
Insensitivity
•Female Appearance
•Male Karyotype
•Testes instead of ovaries
& uterus in abdominal
cavity
•Mutation – makes cells
unable to respond to male
sex hormone.
•The androgen receptor is
ineffective
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Gene Regulation
Carcinogenesis
31
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
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Carcinogenesis
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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