Download Regulation

Prokaryotic Regulation – Operon Model
Precursor
Feedback
inhibition
Operons: The Basic Concept
• “on-off switch”
trpE
Enzyme 1
trpD
Enzyme 2
• Operator
Regulation
of gene
expression
trpC
• Operon
trpB
Enzyme 3
trpA
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Tryptophan
(a) Regulation of enzyme
activity
(b) Regulation of enzyme
production
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• Repressor
• E. coli can synthesize the amino acid
tryptophan when it has insufficient
tryptophan
• Regulatory gene
• Corepressor
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trp operon
DNA
Promoter Regulatory gene
Promoter
mRNA
DNA
Genes of operon
trpE
trpR
3′
RNA
polymerase
trpD
trpC
trpR
trpB
trpE
trpA
Operator
Start codon Stop codon
mRNA
5′
mRNA 5′
No
RNA
made
3′
5′
Protein
Inactive
repressor
D
C
B
A
Tryptophan
(corepressor)
Polypeptide subunits that make up
enzymes for tryptophan synthesis
(a) Tryptophan absent, repressor inactive, operon on
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Active
repressor
Protein
E
(b) Tryptophan present, repressor active, operon off
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1
Negative Gene Regulation
• inducible operon
– lac operon
• repressible operon
– trp operon
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lac operon
DNA
Regulatory
gene
lacI
Promoter
Operator
DNA
lac I
mRNA
5′
Protein
3′
IacZ
No
RNA
made
3′
lacZ
RNA polymerase
mRNA
(a) Lactose absent, repressor active, operon off
lacA
mRNA 5′
5′
Protein
β-Galactosidase
RNA
polymerase
Active
repressor
lacY
Start codon Stop codon
Permease
Transacetylase
Inactive
repressor
Allolactose
(inducer)
(b) Lactose present, repressor inactive, operon on
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Positive Gene Regulation
• Inducible enzymes
• catabolite activator protein (CAP)
• Repressible enzymes
• Regulation of the trp and lac operons
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2
Promoter
Operator
DNA
lac I
Promoter
DNA
lacZ
CAP-binding site
Active
CAP
cAMP
RNA
polymerase
binds and
transcribes
Inactive
CAP
Allolactose
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Operator
RNA
polymerase less
likely to bind
Inactive
CAP
Inactive lac
repressor
(a) Lactose present, glucose scarce (cAMP level high):
abundant lac mRNA synthesized
lacZ
lac I
CAP-binding site
Inactive lac
repressor
(b) Lactose present, glucose present (cAMP level low):
little lac mRNA synthesized
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Figure 18.6a
Eukaryotic gene expression
Signal
Chromatin
Chromatin
modification:
DNA unpacking
DNA
• Differential Gene Expression
Gene available for transcription
Transcription
RNA
Exon
Primary
transcript
Intron
RNA processing
Tail
Cap
NUCLEUS
mRNA in nucleus
Transport to
cytoplasm
CYTOPLASM
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Figure 18.6b
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Regulation of Chromatin Structure
Translation
Polypeptide
Protein processing
Degradation
of protein
Active protein
Transport to cellular
destination
Cellular function
(such as enzymatic
activity or structural
support)
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© 2014 Pearson Education, Inc.
3
Figure 18.7
Histone
tails
Histone Modifications and DNA Methylation
DNA double
helix
Amino acids
available
for chemical
modification
• histone acetylation
Nucleosome
(end view)
(a) Histone tails protrude outward from a nucleosome
Acetyl
groups
• DNA methylation
Unacetylated histones
(side view)
DNA
Acetylated histones
(b) Acetylation of histone tails promotes loose chromatin
structure that permits transcription
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Figure 18.8
Figure 18.8b-3
Proximal
control elements
Enhancer (group of
distal control elements)
Proximal
control elements
DNA
Exon
Upstream
Poly-A signal
sequence
Transcription
start site
Intron
Promoter
Exon
Intron
Transcription
Primary RNA
transcript
5′
(pre-mRNA)
Exon
Intron
Exon
Intron
Exon
Transcription
termination
region
Downstream
Poly-A
signal
Cleaved 3′ end
Exon
of primary
transcript
DNA
Poly-A signal
sequence
Transcription
start site
Exon
Intron
Exon
Exon
Intron
Exon
Promoter
Primary RNA
transcript
5′
(pre-mRNA)
Intron
Poly-A
signal
Transcription
Intron
RNA processing
Intron RNA
Exon
RNA
processing
Intron RNA
Exon
Cleaved
3′ end
of primary
transcript
Coding segment
mRNA
G
P
P
5′ Cap
P
AAA⋯AAA
5′ UTR
Start
codon
Stop
codon
3′ UTR
3′
Poly-A
tail
Coding segment
mRNA G P P P
5′ Cap
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AAA⋯AAA
5′ UTR
Start
codon
Stop
codon
3′ UTR
3′
Poly-A
tail
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Regulation of Transcription Initiation
• control elements
– Proximal control elements
• Activator
– two domains
– Distal control elements
• enhancers
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4
Figure 18.9
DNA
Promoter
Activators
Gene
Enhancer
Distal control
element
TATA
box
General
transcription
factors
DNAbending
protein
Activation
domain
Group of mediator proteins
DNA-binding
domain
DNA
RNA
polymerase II
RNA polymerase II
Transcription
initiation complex
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RNA synthesis
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Figure 18.11
DNA in both cells
contains the albumin
gene and the
crystallin gene:
Control
elements
Enhancer for
albumin gene Promoter
Enhancer for
crystallin gene Promoter
Crystallin gene
Coordinately Controlled Genes
• Co-expressed eukaryotic
LENS CELL NUCLEUS
LIVER CELL NUCLEUS
Available
activators
Available
activators
Albumin gene
not expressed
Albumin
gene
expressed
Crystallin gene
not expressed
(a) Liver cell
Albumin gene
Crystallin
gene expressed
(b) Lens cell
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Post-Transcriptional Regulation
RNA Processing
• alternative RNA splicing
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© 2014 Pearson Education, Inc.
5
Figure 18.13
Initiation of Translation
Exons
1
DNA
2
3
4
5
Troponin T gene
Primary
RNA
transcript
1
2
3
4
5
RNA splicing
mRNA
1
2
3
5
OR
1
2
4
5
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Protein Processing and Degradation
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Noncoding RNAs
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Figure 18.14
miRNA
miRNAprotein
complex
Differential Gene Expression
1 The miRNA binds
to a target mRNA.
OR
mRNA degraded
Translation blocked
2 If bases are completely complementary, mRNA is degraded.
If match is less than complete, translation is blocked.
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6
Cytoplasmic Determinants
Zygote  Adult
• Cytoplasmic determinants
• Cell differentiation
• Morphogenesis
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Figure 18.17
Inductive Signals
• Induction
(a) Cytoplasmic determinants in the egg
(b) Induction by nearby cells
Molecules of two different
cytoplasmic determinants
Early embryo
(32 cells)
Nucleus
Fertilization
Unfertilized
egg
Sperm
NUCLEUS
Mitotic cell
division
Signal
transduction
pathway
Zygote
(fertilized egg)
Signal
receptor
Two-celled
embryo
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Signaling
molecule
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Figure 18.17a
Figure 18.17b
(b) Induction by nearby cells
(a) Cytoplasmic determinants in the egg
Early embryo
(32 cells)
Molecules of two different
cytoplasmic determinants
Nucleus
Fertilization
Unfertilized
egg
Sperm
NUCLEUS
Mitotic cell
division
Signal
transduction
pathway
Signal
receptor
Zygote
(fertilized egg)
Two-celled
embryo
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Signaling
molecule
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7
Sequential Regulation
Nucleus
Master regulatory gene myoD
Embryonic
precursor cell
• Determination
Other muscle-specific genes
DNA
OFF
OFF
OFF
mRNA
Myoblast
(determined)
MyoD protein
(transcription
factor)
mRNA
MyoD
Part of a muscle fiber
(fully differentiated cell)
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mRNA
Another
transcription
factor
mRNA
mRNA
Myosin, other
muscle proteins,
and cell cycle–
blocking proteins
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Figure 18.19b-5
Follicle cell
1 Developing
egg within
ovarian
follicle
Cancer
Nucleus
Egg
Nurse cell
Egg
shell
2 Mature,
unfertilized
egg
Depleted
nurse cells
Fertilization
Laying of egg
3 Fertilized
egg
Embryonic
development
4 Segmented
embryo
0.1 mm
Body
segments
Hatching
5 Larva
(b) Development from egg to larva
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Types of Genes Associated with Cancer
• Proto-oncogenes can be converted to
oncogenes by
• Oncogenes
• Proto-oncogenes
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8
Figure 18.23
Tumor-Suppressor Genes
Proto-oncogene
Translocation or
transposition: gene
moved to new locus,
under new controls
Oncogene
Normal growth-stimulating
protein in excess
• Tumor-suppressor genes
Point mutation:
Gene amplification:
multiple copies of
the gene
New promoter
Normal growthstimulating
protein in excess
Proto-oncogene
Proto-oncogene
within a control
element
within the gene
Oncogene
Oncogene
Normal growthstimulating protein
in excess
• Tumor-suppressor proteins
Hyperactive or
degradationresistant
protein
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Interference with Normal CellSignaling Pathways
• Mutations in the ras proto-oncogene
Figure 18.24
1 Growth factor
3 G protein
P
P
P
P
P
P
NUCLEUS
Ras
GTP
2 Receptor
5
Transcription
factor (activator)
6 Protein that
stimulates
the cell cycle
4 Protein
kinases
• Mutations in p53 tumor-suppressor gene
MUTATION
Ras
GTP
NUCLEUS
Overexpression
of protein
Transcription
factor (activator)
Ras protein active
with or without
growth factor.
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Figure 18.25
Inherited Predisposition
2 Protein kinases
5 Protein that
NUCLEUS
inhibits the
cell cycle
UV
light
1 DNA damage
in genome
3 Active form
4 Transcription
of p53
• colorectal cancer
Inhibitory
protein
absent
UV
light
MUTATION
DNA damage
in genome
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• Individuals can inherit oncogenes or
mutant alleles of tumor-suppressor genes
• breast cancers
Defective or
missing
transcription
factor.
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9
The Role of Viruses in Cancer
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10