CONTROL

OF GENE
EXPRESSION
 INTRO-
DUCTION
 • The transcription of a gene into mRNA and its
subsequent translation into protein
• The creation of a protein from its gene
• Gene expression is primarily controlled at the
level of transcription, largely as a result of
binding of proteins to specific sites on DNA

GENE
EXPRESSION
 • Controlling gene expression is critical to a cell
because it allows it to avoid wasting energy
and raw materials in the synthesis of proteins
it does not need
• It allows a cell to be a more streamlined and
versatile entity that can respond to changing
conditions by adjusting its physiology

GENE
EXPRESSION
 • Prokaryotes and eukaryotes alter gene
expression in response to their changing
environment
• In multicellular eukaryotes, gene expression
regulates development and is responsible for
differences in cell types
• RNA molecules play many roles in regulating
gene expression in eukaryotes

GENE
EXPRESSION
BACTERIA OFTEN
RESPOND TO
ENVIRONMENTAL
CHANGE BY
REGULATING
TRANSCRIPTION
• Natural selection has favored bacteria that produce
only the products needed by that cell
• A cell can regulate the production of enzymes by
feedback inhibition or by gene regulation
• Gene expression in bacteria is controlled by the
operon model

TRANSCRIPTION
W H I C H S TA G E
DOES GENE
EXPRESSION
CONTROL
OCCURS?
Gene expression is primarily
controlled at the level of
transcription, the process of
making a messenger
ribonucleic acid (mRNA)
copy of the deoxyribonucleic
acid (DNA) gene
OPERONS:
THE BASIC
CONCEPT
 • A cluster of functionally related genes can
be under coordinated control by a single
on-off “switch”
• The regulatory “switch” is a segment of
DNA called an operator usually positioned
within the promoter
• An operon is the entire stretch of DNA that
includes the operator, the promoter, and the
genes that they control

OPERONS
 • The operon can be switched off by a protein
repressor
• The repressor prevents gene transcription by
binding to the operator and blocking RNA
polymerase
• The repressor is the product of a separate
regulatory gene

OPERONS
 • The repressor can be in an active or inactive
form, depending on the presence of other
molecules
• A corepressor is a molecule that cooperates with
a repressor protein to switch an operon off
• For example, E. coli can synthesize the amino
acid tryptophan

OPERONS
 • By default the trp operon is on and the
genes for tryptophan synthesis are
transcribed
• When tryptophan is present, it binds to
the trp repressor protein, which turns the
operon off
• The repressor is active only in the
presence of its corepressor tryptophan;
thus the trp operon is turned off
(repressed) if tryptophan levels are high

OPERONS
Fig. 18-3a

trp operon
Promoter Promoter
Genes of operon
DNA trpR trpE trpD trpC trpB trpA
Regulatory Operator
gene Start codon Stop codon
3
mRNA RNA mRNA 5
5 polymerase E D C B A
Protein Inactive Polypeptide subunits that make up
repressor enzymes for tryptophan synthesis
(a) Tryptophan absent, repressor inactive, operon on
Fig. 18-3b-1

DNA
No RNA made

mRNA

Protein Active
repressor
Tryptophan
(corepressor)
(b) Tryptophan present, repressor active, operon off
Fig. 18-3b-2

DNA
No RNA made

mRNA

Protein Active
repressor
Tryptophan
(corepressor)
(b) Tryptophan present, repressor active, operon off
REGRESSIBLE &
INDUCIBLE OPERONS:
TWO TYPES OF
NEGATIVE GENE
REGULATION
• A repressible operon is one that is usually on; binding
of a repressor to the operator shuts off transcription
• The trp operon is a repressible operon
• An inducible operon is one that is usually off; a
molecule called an inducer inactivates the repressor
and turns on transcription

NEGATIVE GENE
REGULATION
Fig. 18-UN2

Genes expressed Genes not expressed

Promoter
Genes

Operator Active repressor:

Inactive repressor: corepressor bound
Corepressor
no corepressor present

REPRESSIBLE OPERON
Fig. 18-UN3

Genes not expressed Genes expressed

Promoter
Operator Genes
Fig. 18-UN2

Active repressor: Inactive repressor:

no inducer present inducer bound

INDUCIBLE OPERON
• The lac operon is an inducible operon and contains
genes that code for enzymes used in the hydrolysis
and metabolism of lactose
• By itself, the lac repressor is active and switches the
lac operon off
• A molecule called an inducer inactivates the
repressor to turn the lac operon on

NEGATIVE GENE
REGULATION
Fig. 18-4 Regulatory Promoter
gene Operator
DNA lacI lacZ
No
RNA
3 made
mRNA RNA
5 polymerase

Active
Protein repressor
(a) Lactose absent, repressor active, operon off
lac operon

DNA lacI lacZ lacY lacA

RNA
3 polymerase
mRNA mRNA 5
5

Protein -Galactosidase Permease Transacetylase

Allolactose Inactive
(inducer) repressor
(b) Lactose present, repressor inactive, operon on
Fig. 18-4a

Regulatory Promoter
gene Operator
DNA lacI lacZ
No
RNA
3 made
mRNA RNA
5 polymerase

Active
Protein repressor
(a) Lactose absent, repressor active, operon off
Fig. 18-4b

lac operon

DNA lacI lacZ lacY lacA

RNA
3 polymerase
mRNA mRNA 5
5

Protein -Galactosidase Permease Transacetylase

Allolactose Inactive
(inducer) repressor
(b) Lactose present, repressor inactive, operon on
• Inducible enzymes usually function in catabolic pathways;
their synthesis is induced by a chemical signal
• Repressible enzymes usually function in anabolic
pathways; their synthesis is repressed by high levels of
the end product
• Regulation of the trp and lac operons involves negative
control of genes because operons are switched off by the
active form of the repressor

NEGATIVE GENE
REGULATION
 POSITIVE
GENE
REGULATION
 • Some operons are also subject to positive
control through a stimulatory protein, such as
catabolite activator protein (CAP), an activator
of transcription
• When glucose (a preferred food source of E.
coli) is scarce, CAP is activated by binding
with cyclic AMP

POSITIVE GENE
REGULATION
 • Activated CAP attaches to the promoter of the lac
operon and increases the affinity of RNA
polymerase, thus accelerating transcription
• When glucose levels increase, CAP detaches
from the lac operon, and transcription returns to a
normal rate
• CAP helps regulate other operons that encode
enzymes used in catabolic pathways

POSITIVE GENE
REGULATION
Fig. 18-5
Promoter
Operator
DNA lacI lacZ
CAP-binding site RNA
polymerase
Active binds and
cAMP CAP transcribes
Inactive Inactive lac
CAP repressor
Allolactose
(a) Lactose present, glucose scarce (cAMP level
high): abundant lac mRNA synthesized
Promoter Operator
DNA lacI lacZ
CAP-binding site RNA
polymerase less
Inactive likely to bind
CAP Inactive lac
repressor
(b) Lactose present, glucose present (cAMP level
low): little lac mRNA synthesized
W H AT I S T H E
DIFFERENCE
BETWEEN
POSITIVE &
N E G AT I V E
GENE
R E G U L AT I O N ?
 POSITIVE VS NEGATIVE GENE REGULATION
Positive gene regulation is a Negative gene regulation is a
process which makes the genes process which represses gene
express and synthesize proteins. expression.

FACTORS INVOLVED
Positive control is done by Negative control is done by the
activator or the transcription repressor protein binding to the
factor binding with the promoter promoter or operator site of the
region. genes.
RECRUITMENT OF RNA POLYMERASE
RNA polymerase is recruited to RNA polymerase is not recruited
initiate transcription. to initiate transcription.
PROKARYOTIC
GENE
EXPRESSION
• Prokaryotic organisms are single-celled organisms that
lack a cell nucleus, and their DNA therefore floats freely
in the cell cytoplasm.
• To synthesize a protein, the processes of transcription
and translation occur almost simultaneously.
• When the resulting protein is no longer needed,
transcription stops.

PROKARYOTES
• As a result, the primary method to control what type of
protein and how much of each protein is expressed in a
prokaryotic cell is the regulation of DNA transcription.
• All of the subsequent steps occur automatically. When
more protein is required, more transcription occurs.

PROKARYOTES
Therefore, in prokaryotic cells, the
control of gene expression is
mostly at the transcriptional level.

PROKARYOTES
EUKARYOTIC
GENE
EXPRESSION
 • Eukaryotic cells, in contrast, have intracellular
organelles that add to their complexity. In
eukaryotic cells, the DNA is contained inside the
cell’s nucleus and there it is transcribed into RNA.
The newly synthesized RNA is then transported
out of the nucleus into the cytoplasm, where
ribosomes translate the RNA into protein. The
processes of transcription and translation are
physically separated by the nuclear membrane;
transcription occurs only within the nucleus, and
translation occurs only outside the nucleus in the
cytoplasm.

EUKARYOTES
 • The regulation of gene expression can occur at all
stages of the process. Regulation may occur
when the DNA is uncoiled and loosened from
nucleosomes to bind transcription factors
(epigenetic level), when the RNA is transcribed
(transcriptional level), when the RNA is processed
and exported to the cytoplasm after it is
transcribed (post-transcriptional level), when the
RNA is translated into protein (translational level),
or after the protein has been made (post-
translational level).

EUKARYOTES
W H AT I S T H E
DIFFERENCE
BETWEEN
EUKARYOTIC
AND
PROKARYOTI
CGENE
EXPRESSION?
 PROKARYOTIC ORGANISMS EUKARYOTIC ORGANISMS
Lack nucleus Contain nucleus
DNA is confined to the nuclear
DNA is found in the cytoplasm
compartment
RNA transcription occurs prior to
RNA transcription and protein protein formation, and it takes place in
formation occur almost simultaneously the nucleus. Translation of RNA to
protein occurs in the cytoplasm.
Gene expression is regulated at many
Gene expression is regulated primarily levels (epigenetic, transcriptional,
at the transcriptional level nuclear shuttling, post-transcriptional,
translational, and post-translational)
M U TAT I O N S C A N
AFFECT PROTEIN
STRUCTURE AND
FUNCTION
• Mutations are changes in the genetic material of a cell
or virus
• Point mutations are chemical changes in just one base
pair of a gene
• The change of a single nucleotide in a DNA template
strand can lead to the production of an abnormal protein

MUTATIONS
• Point mutations within a gene can be divided into two
general categories
• Nucleotide-pair substitutions
• One or more nucleotide-pair insertions or deletions

TYPES OF
SMALL-SCALE
MUTATIONS
• A nucleotide-pair substitution replaces one nucleotide
and its partner with another pair of nucleotides
• Silent mutations have no effect on the amino acid
produced by a codon because of redundancy in the
genetic code

SUBSTITUTIONS
• Missense mutations still code for an amino acid, but not
the correct amino acid
• Nonsense mutations change an amino acid codon into a
stop codon, nearly always leading to a nonfunctional
protein

SUBSTITUTIONS
• Insertions and deletions are additions or losses of
nucleotide pairs in a gene
• These mutations have a disastrous effect on the
resulting protein more often than substitutions do
• Insertion or deletion of nucleotides may alter the reading
frame, producing a frameshift mutation

INSERTIONS &
DELETIONS
• Spontaneous mutations can occur during DNA
replication, recombination, or repair
• Mutagens are physical or chemical agents that can
cause mutations

MUTAGENS
THE END!
ABOGADO
ASIS
C A N T U TAY
ESPENIDO
SALISE
VA S Q U E Z
X - PROTON