Transcript 11_Lecture_Presentation

Chapter 11
How Genes Are Controlled
PowerPoint Lectures for
Biology: Concepts & Connections, Sixth Edition
Campbell, Reece, Taylor, Simon, and Dickey
Lecture by Mary C. Colavito
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CONTROL OF GENE
EXPRESSION
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Gene expression is the overall process of
information flow from genes to proteins
– Mainly controlled at the level of transcription
– A gene that is “turned on” is being transcribed to
produce mRNA that is translated to make its
corresponding protein
– Organisms respond to environmental changes by
controlling gene expression
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 An operon is a group of genes under coordinated
control in bacteria
 The lactose (lac) operon includes
– Three adjacent genes for lactose-utilization enzymes
– Promoter sequence where RNA polymerase binds
– Operator sequence is where a repressor can bind
and block RNA polymerase action
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Regulation of the lac operon
– Regulatory gene codes for a repressor protein
– In the absence of lactose, the repressor binds to the
operator and prevents RNA polymerase action
– Lactose inactivates the repressor, so the operator is
unblocked
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11.1 Proteins interacting with DNA turn
prokaryotic genes on or off in response to
environmental changes
 Types of operon control
– Inducible operon (lac operon)
– Active repressor binds to the operator
– Inducer (lactose) binds to and inactivates the repressor
– Repressible operon (trp operon)
– Repressor is initially inactive
– Corepressor (tryptophan) binds to the repressor and
makes it active
– For many operons, activators enhance RNA
polymerase binding to the promoter
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An example of gene regulation – the Lac Operon
Lac Operon Animation
OPERON
Regulatory Promoter Operator
gene
Lactose-utilization genes
DNA
mRNA
Protein
RNA polymerase
cannot attach to
promoter
Active
repressor
Operon turned off (lactose absent)
DNA
mRNA
RNA polymerase
bound to promoter
Protein
Lactose
Inactive
repressor
Operon turned on (lactose inactivates repressor)
Enzymes for lactose utilization
OPERON
Regulatory Promoter Operator
gene
Lactose-utilization genes
DNA
mRNA
Protein
Active
repressor
Operon turned off (lactose absent)
RNA polymerase
cannot attach to
promoter
DNA
mRNA
RNA polymerase
bound to promoter
Protein
Lactose
Inactive
repressor
Enzymes for lactose utilization
Operon turned on (lactose inactivates repressor)
Promoter Operator
Gene
DNA
Active
repressor
Active
repressor
Tryptophan
Inactive
repressor
Inactive
repressor
Lactose
lac operon
trp operon
11.2 Differentiation results from the expression
of different combinations of genes
 Differentiation involves cell specialization, in
both structure and function
 Differentiation is controlled by turning specific
sets of genes on or off
 This is how we get cells that have the same
genetic information, but different structures and
functions
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Muscle cell
Pancreas cells
Blood cells
Metaphase
chromosome
Tight helical fiber
(30-nm diameter)
DNA double helix
(2-nm diameter)
Linker
“Beads on
a string”
Nucleosome
(10-nm
diameter)
Histones
Supercoil
(300-nm diameter)
700 nm
11.3 DNA packing in eukaryotic chromosomes
helps regulate gene expression
 Eukaryotic chromosomes undergo multiple levels
of folding and coiling, called DNA packing
– Nucleosomes are formed when DNA is wrapped
around histone proteins
– “Beads on a string” appearance
– Each bead includes DNA plus 8 histone molecules
– String is the linker DNA that connects nucleosomes
– Tight helical fiber is a coiling of the nucleosome
string
– Supercoil is a coiling of the tight helical fiber
– Metaphase chromosome represents the highest level
of packing
 DNA packing can prevent transcription
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11.3 DNA packing in eukaryotic chromosomes
helps regulate gene expression
Animation: DNA Packing
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11.4 In female mammals, one X chromosome is
inactive in each somatic cell
 X-chromosome inactivation
– In female mammals, one of the two X chromosomes
is highly compacted and transcriptionally inactive
– Random inactivation of either the maternal or
paternal chromosome
– Occurs early in embryonic development and all
cellular descendants have the same inactivated
chromosome
– Inactivated X chromosome is called a Barr body
– Tortoiseshell fur coloration is due to inactivation of X
chromosomes in heterozygous female cats
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Early embryo
Two cell populations
in adult
Cell division
and random
X chromosome
inactivation
X chromosomes
Allele for
orange fur
Allele for
black fur
Active X
Inactive X
Orange
fur
Inactive X
Active X
Black fur
11.5 Complex assemblies of proteins control
eukaryotic transcription
 Eukaryotic genes
– Each gene has its own promoter and terminator
– Are usually switched off and require activators to be
turned on
– Are controlled by interactions between numerous
regulatory proteins and control sequences
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11.5 Complex assemblies of proteins control
eukaryotic transcription
 Regulatory proteins that bind to control
sequences
– Transcription factors promote RNA polymerase
binding to the promoter
– Activator proteins bind to DNA enhancers and
interact with other transcription factors
– Silencers are repressors that inhibit transcription
 Control sequences
– Promoter
– Enhancer
– Related genes located on different chromosomes can be
controlled by similar enhancer sequences
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11.5 Complex assemblies of proteins control
eukaryotic transcription
Animation: Initiation of Transcription
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Enhancers
Promoter
Gene
DNA
Activator
proteins
Transcription
factors
Other
proteins
RNA polymerase
Bending
of DNA
Transcription
11.6 Eukaryotic RNA may be spliced in more
than one way
 Alternative RNA splicing
– Production of different mRNAs from the same
transcript
– Results in production of more than one polypeptide
from the same gene
– Can involve removal of an exon with the introns on
either side
Animation: RNA Processing
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Exons
1
DNA
RNA
transcript
1
1
2 3
5
4
3
2
RNA splicing
mRNA
4
3
2
5
or
5
1
2 4
5
11.8 Translation and later stages of gene
expression are also subject to regulation
 Control of gene expression also occurs with
– Breakdown of mRNA
– Initiation of translation
– Protein activation
– Protein breakdown
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Folding of
polypeptide and
formation of
S—S linkages
Initial polypeptide
(inactive)
Cleavage
Folded polypeptide
(inactive)
Active form
of insulin
11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
 Many possible control points exist; a given gene
may be subject to only a few of these
– Chromosome changes (1)
– DNA unpacking
– Control of transcription (2)
– Regulatory proteins and control sequences
– Control of RNA processing
– Addition of 5’ cap and 3’ poly-A tail (3)
– Splicing (4)
– Flow through nuclear envelope (5)
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11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
 Many possible control points exist; a given gene
may be subject to only a few of these
– Breakdown of mRNA (6)
– Control of translation (7)
– Control after translation
– Cleavage/modification/activation of proteins (8)
– Breakdown of protein (9)
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11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
 Applying Your Knowledge
For each of the following, determine whether an
increase or decrease in the amount of gene
product is expected
– The mRNA fails to receive a poly-A tail during
processing in the nucleus
– The mRNA becomes more stable and lasts twice as
long in the cell cytoplasm
– The region of the chromatin containing the gene
becomes tightly compacted
– An enzyme required to cleave and activate the
protein product is missing
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11.9 Review: Multiple mechanisms regulate gene
expression in eukaryotes
Animation: Protein Degradation
Animation: Protein Processing
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NUCLEUS
Chromosome
DNA unpacking
Other changes to DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of cap and tail
Splicing
Tail
mRNA in nucleus
Cap
Flow through
nuclear envelope
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Translation
Brokendown
mRNA
Polypeptide
Cleavage / modification /
activation
Active protein
Breakdown
of protein
Brokendown
protein
NUCLEUS
Chromosome
DNA unpacking
Other changes to DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of cap and tail
Splicing
Tail
mRNA in nucleus
Cap
Flow through
nuclear envelope
mRNA in cytoplasm
CYTOPLASM
Breakdown of mRNA
Translation
Brokendown
mRNA
Polypeptide
Cleavage / modification /
activation
Active protein
Breakdown
of protein
Brokendown
protein
11.10 Cascades of gene expression direct the
development of an animal
 Role of gene expression in fruit fly development
– Orientation from head to tail
– Maternal mRNAs present in the egg are translated and
influence formation of head to tail axis
– Segmentation of the body
– Protein products from one set of genes activate other sets
of genes to divide the body into segments
– Production of adult features
– Homeotic genes are master control genes that
determine the anatomy of the body, specifying structures
that will develop in each segment
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11.10 Cascades of gene expression direct the
development of an animal
Animation: Cell Signaling
Animation: Development of Head-Tail Axis in Fruit Flies
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Eye
Antenna
Leg
Head of a normal fruit fly
Head of a developmental mutant
Eye
Antenna
Head of a normal fruit fly
Leg
Head of a developmental mutant
Egg cell
Egg cell
within ovarian
follicle
Protein
signal
Follicle cells
1
Gene expression
“Head”
mRNA
2
Embryo
3
Cascades of
gene expression
Body
segments
Gene expression
Adult fly
4
11.11 CONNECTION: DNA microarrays test for
the transcription of many genes at once
 DNA microarray
– Contains DNA sequences arranged on a grid
– Used to test for transcription
– mRNA from a specific cell type is isolated
– Fluorescent cDNA is produced from the mRNA
– cDNA is applied to the microarray
– Unbound cDNA is washed off
– Complementary cDNA is detected by fluorescence
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DNA microarray
Actual size
(6,400 genes)
Each well contains DNA
from a particular gene
1
mRNA
isolated
Reverse transcriptase
and fluorescent DNA
nucleotides
2
cDNA made
from mRNA
4
3
Unbound
cDNA rinsed
away
cDNA applied
to wells
Fluorescent
spot
Nonfluorescent
spot
cDNA
DNA of an
DNA of an
expressed gene unexpressed gene
THE GENETIC BASIS
OF CANCER
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11.18 Cancer results from mutations in genes
that control cell division
 Mutations in two types of genes can cause cancer
– Oncogenes
– Proto-oncogenes normally promote cell division
– Mutations to oncogenes enhance activity
– A faulty p53 gene causes cancer
– Tumor-suppressor genes
– Normally inhibit cell division
– Mutations inactivate the genes and allow uncontrolled
division to occur
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You should now be able to
1. Explain how prokaryotic gene control occurs in
the operon
2. Describe the control points in expression of a
eukaryotic gene
3. Describe DNA packing and explain how it is
related to gene expression
4. Explain how alternative RNA splicing and
microRNAs affect gene expression
5. Compare and contrast the control mechanisms
for prokaryotic and eukaryotic genes
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You should now be able to
6. Distinguish between terms in the following
groups: promoter—operator; oncogene—tumor
suppressor gene; reproductive cloning—
therapeutic cloning
7. Define the following terms: Barr body,
carcinogen, DNA microarray, homeotic gene;
stem cell; X-chromosome inactivation
8. Describe the process of signal transduction,
explain how it relates to yeast mating, and
explain how it is disrupted in cancer development
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You should now be able to
9. Explain how cascades of gene expression affect
development
10. Compare and contrast techniques of plant and
animal cloning
11. Describe the types of mutations that can lead to
cancer
12. Identify lifestyle choices that can reduce cancer
risk
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