Control of Gene Expression

Control of Gene
Expression
Deniz Ağırbaşlı M.D. Ph.D., Assist Prof.

MED 111
2017-2018
By the end of this lecture, you will be able to;
• Define gene expression

• Explain control of gene expression in prokaryotes
vs eukaryotes
• Define operon model and how it differentiates
form eukaryotic control
• Explain the lac operon and trp orperon
• Gene Expression (Gene Expression) is the
process by which genes are converted into
functional proteins.
• Gene regulation is control of structures and
functions, which constitute the basis of cell
differentiation, morphogenesis and versatile
adaptation in living organisms
• Cell differentiation occurs without a change in
the DNA sequence
• Both have the same genome but they express
different sets of RNAs and proteins
Comparison of two gene expressions and house
keeping genes
6 steps of eucaryotic gene expression
control
The transcriptional control
• Approx. 10% of the protein coding genes of
most organisms are devoted to transcription
regulation
• One of the largest protein classes in the cell
• They bind to DNA as cis regulatory sequences
• They determine which gene will be
transcribed
Control of GE in Prokaryotes
Why is it different in prokaryotes
• Prokaryotes have to respond very quickly to
the environmental stimuli.
• Half life of mRNA is short (1-2 min)
• Transcription and translation happens in the
same compartment. Major control is the
transcriptional control.
Regulatory Genes
• 1. Turns on the expression of one /more genes
• 2. Turns off the expression of one /more genes
monocystronic vs polycystronic
mRNA synthesizes one polypeptide in eucaryotes,
but in prokaryotes one mRNA synthesizes more than
one polypeptide.
This is explained in operon model
Operon is a unit of expression and regulation.
Monocystronic vs polycystronic
One promoter many/one polipeptide
Plasticity: Mechanisms that involve the rapis turn-on and turn-off gene
expression in response to environmental stimuli
Proper sequence of events: Ability to reprogram circuits in the system

by following an order
• Housekeeping genes
• Inducable Genes
• Repressible genes
Operon Model (Jacob and Monod 1960)
• The Nobel Prize in Physiology or Medicine 1965

was awarded jointly to François Jacob, André
Lwoﬀ and Jacques Monod "for their discoveries
concerning genetic control of enzyme and virus
synthesis".
https://www.ncbi.nlm.nih.gov/books/NBK2168
3/
Operon Model
• Structural genes: polycystronic genes
encoding enzymes synthesized from single
mRNA and promoter
• Operator: regulatory protein binding region
adjecent to promoter
• Regulatory gene: positive or negative
regulation
• In positive control regulators are activators, in
negative control regulators are repressors
Effector molecules
• Effector molecules control regulatory
proteins to bind RPBR.
• Inductors
• Co-repressors
Allosteric Effects
• Effector molecules bind regulatory proteins
and make a conformational change in the
protein. This is allosteric effect.
• Allosteric changes caused by binding of the

effector molecules to activators or inhibitors
alter the ability to bind to RPBS.
Lac operon: What is lactose?
Gene expression is
induced when there is
plenty of lactose and no
glucose
In catabolic pathways,
enzymes are induced
Lac operon is an inducable operon
usually it is turned off
• A-STRUCTURAL GENES
1. beta galaktosidase- “z gene”: catabolises lactose into
glucose+gal actose or allolactose
2. beta galaktoside permease-“y gene”: allows the lactose to
be taken into the cell
3. beta galaktoside acetyl transferase-“a gene”: elimination of
by-products of lactose metabolism
All is controlled by the same promoter
• B- REGULATOR GENE
• Upstream of lac operon, i gene (inducer) codes for repressor
protein which binds to the operator region of lac operon
How is lac operon controlled?
• Glucose (+), Lactose (-) medium

Plenty of glucose, repressor is bound to operator,
operon is closed. No transcription.
• Glucose (-), Lactose (+) medium
• Enzymes in Lac operon synthesize allolactose from
lactose Allolactose is an inducer of lac operon. It binds
to repressor and make a confirmational change in
repressor so that it cannot bind to the operator. Then
RNA polimerase binds to promoter and transcription
begins.
• Glucose (+), Lactose (+) medium
Transcription happens for there is allolactose as
an inducer
However, the transcription level is very low,
almost suppressed. Because glucose levels are
high and therefore the levels of cAMP are low.
• As glucose decreases, if there is still lactose in
the medium, operon lets the transcription
activated
• How cAMP activates lac operon:
cAMP (hunger signal) allosterically binds CAP
(catabolic activator protein). CAP binds to
promoter and transcription is activated.
cAMP is the activator of operon
cAMP control
• Glucose inhibits adenyl cyclase activity and decreases
cAMP in the cell.
• CAP-cAMP complex which is necessary for
transcription is not formed
Tryptophan operon
• Tryptophan codes for anabolic enzymes.
(precursor of melatonin and seratonin)
• It is transcribed only if there is a need.
• For humans it is one of the essential aa.
• Trp operon in bacteria: when we eat a food
rich in tryptophan, the trp operon is
suppressed in bacteria in the intestines.
Transcription is induced only if
tryptophan is not in the
medium.
If there is a plenty of
tryptophan, the transcription
is supressed.
Enzymes in anabolic pathways

are usually repressible
Trp operon is a repressible operon, usually
it is turned on
Differences from lac operon
• In this system, unlike the lac operon, the
repressor gene is not in close proximity to the
promoter. On the contrary, it is localized in a
different place of the E. Coli genome.
• In contrast to the induced system, the trp
operon is usually transcriptionally open.

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Control of Gene

Deniz Ağırbaşlı M.D. Ph.D., Assist Prof.

• Define gene expression

Proper sequence of events: Ability to reprogram circuits in the system

• The Nobel Prize in Physiology or Medicine 1965

• Allosteric changes caused by binding of the

• Glucose (+), Lactose (-) medium

Enzymes in anabolic pathways

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