Control Mechanisms
Gene Regulation
Gene Regulation
 ~ 42,000 genes exist that code for proteins in
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humans
Not all proteins are required all the time
Example: Insulin only required when glucose level
is high
Gene Regulation is a mechanism turning on or off of
specific genes depending on the requirements of the
organism
Gene regulation is vital to an organism’s survival
Housekeeping Genes
 Genes that are switched on all the time because they are
always needed in the cell for life functions
 These genes are constantly transcribed and translated
Transcription Factors
 Proteins that switch
on genes by binding
to DNA and helping
the RNA polymerase
to bind
 Turn on genes when
required
Four Leves of Control of Gene
Expression
In Eukaryotic Cells
1. Transcriptional Control
2. Post transcriptional Control
3. Translational Control
4. Post translational Control
1. Transcriptional Control
• It regulates which genes
are transcribed (DNA
or mRNA) or
• Controls the rate at
which transcription
occurs
2. Posttranscriptional Control
The mRNA molecules undergo
changes in the nucleus before
translation occurs
Introns are removed and exons are
spliced together
3. Translational Control
• It controls how often and how
rapidly mRNA transcripts
will be translated into
proteins
• This control affects the length
of time it takes for mRNA to
be activated and the speed at
which cytoplasmic enzymes
destroy mRNA
4. Posttranslational Control
• Before many proteins become
functional, they must pass
through the cell membrane.
• A number of control mechanisms
affect the rate at which a protein
becomes active and the time that
it remains functional, including
the addition of various chemical
groups
Gene Regulation Mechanisms
Two important regulatory mechanisms:
Induction
Repression
Operons
 Cluster of genes, often functionally related, forming a tight
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cluster on the genome
Primarily occurring in prokaryotes (such as bacteria)
Also some in eukaryotes
Controlled by a common ‘ON/OFF’ switch
Operons are under the control of regulatory elements and
factors that bind to these elements.
What are these elements?
Operons
Promoter
• A DNA sequence that enables a gene
to be transcribed
• Recognized by RNA polymerase,
which then initiates transcription.
Operator
• A segment of DNA that a regulatory protein
binds to.
• Classically defined in the lac operon as a
segment between the promoter and the genes
of the operon
• A repressor or activator can bind to an
operator.
Operons
 Transcription of the cluster results in a single molecule,
 The molecule is a multi-gene transcript of mRNA
 It codes for several proteins and is
 directly translated into distinct protein products.
Operon Gene Regulation
 Control of an operon is a type of gene regulation that enables
organisms to regulate the expression of various genes
depending on environmental conditions.
 Operon regulation can be either negative or positive by
induction or repression.
Operon Gene Regulation
•Positive
gene
Induction
regulation
•Negative
gene
Repression
regulation
Operon Gene Regulation
 Induction and repression respond to specific substances,
called effectors
 Effectors control the activity of a specific set of genes
The lac Operon
 The lac operon is a cluster of genes of the model bacterium
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Escherichia coli
The first operon to be discovered
The lac operon is regulated by several factors including the
availability of glucose and lactose.
It consists of a promoter, an operator, followed by a group of
lactose-utilizing genes
Promoter: the binding site of RNA polymerase.
Operator: regulatory sequence that act as switch.
Lactose
 A disaccharide found in milk or milk products
 Consists of two sugars: glucose and galactose
 E coli found on the intestinal lining of mammals can use the
energy supplied by lactose for growth
 To use the energy, E coli must split lactose into its two
monomer sugars
Glucose
Galactose
Escherichia coli
 E coli produces an enzyme to degrade lactose
 Enzyme called β-galactosidase
 There is no need for E coli to produce this enzyme at
all times
 It only produces the enzyme when lactose is present
 E coli uses negative regulation to control the
transcription and translation of the β-galactosidase
gene
Negative control system
Presence
of Lactose
• Production of βgalactosidase starts if
lactose is present
Absence
of Lactose
• Production of βgalactosidase is blocked
if lactose is absent
The lac Operon
lac Z
 The lactose-utilizing genes are:
lacY
lac A
 lac Z, lacY, and lac A
 lac Z gene encodes the enzyme β-galactosidase
 lacY gene encodes β-galactosidase permease (an
enzyme that causes lactose to permeate the cell
membrane and enter the cell)
 lac A gene encodes a transacetylase (function unknown)
Lacl Protein:
 A repressor protein
 Blocks the transcription of the β-galactosidase gene
 It does that by binding to the Lactose operator and getting
in the way of the RNA polymerase
(Repressor protein: regulatory molecule binding to an
operator site and preventing transcription of an operon)
When lactose is not present
 The promoter and operator regions overlap
 When the Lacl protein binds to the operator, it converts part
of the promoter, which is the binding site for RNA
polymerase
When lactose is present
 The presence of lactose removes Lacl protein (repressor)
 Therefore, lactose is known as the signal molecule or an inducer
Signal
molecule
• a molecule that activates an
activator protein or represses a
repressor protein
Inducer
• A molecule that binds to a
repressor protein and causes a
change in conformation
• This results in the repressor
protein falling off the operator
Protein Transcription
 Lactose binds to the Lacl protein changing the conformation
of the Lacl protein
 This change results in the inability of the new complex to
stay bound to the operator region of the lac operon
 The complex falls off the DNA allowing RNA polymerase to
proceed onward and transcribe the lac operon
 In the case of the lac
Operon, the level of
lactose is an effector,
meaning that it controls
the activity of a
specific set of genes
 The lac Operon is
an example of enzyme
induction
Operon Gene Regulation
•Positive
gene
Induction
regulation
•Negative
gene
Repression
regulation
The trp Operon
 Another example of coordinated regulation
 In contrast to the lac Operon (transcription induced with
presence of lactose), the trp Operon is repressed when high
levels of tryptophan are present.
 In this case, the effector is the level of tryptophan
 Tryptophan is an amino acid that is used by E coli cells for
the production of protein
 E coli cells located on the intestinal lining of a mammal can
absorb tryptophan from the mammal’s diet
The trp Operon
 Consists of five genes
 These five genes code for five polypeptides that make three
enzymes needed to synthesize tryptophan
Corepressor
 Since tryptophan itself is needed to inactivate the trp operon,
it is called a corepressor
 Corepressor:
- a molecule that binds to a repressor to activate it
- usually the product of an operon
When Tryptophan Level is low
 When the level of tryptophan is low, the shape of the trp pressor
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protein changes
This is due to the lack of tryptophan corepressor
The trp repressor can no longer stay bound to the trp operator
and it falls off
The RNA polymerase is free to transcribe the trp operon genes
This results in an increase in tryptophan production
When Tryptophan Level is high
 The amino acid tryptophan binds to the trp repressor
protein, altering its shape
 The trp-repressor-tryptophan complex can now bind to the
trp operator
 This way transcription is blocked
Comparison of the two
Operons
 lac Operon
 The lacl repressor protein
binds to the operator when
lactose levels are low
 High level of lactose induce
the operon
 trp Operon
 The corepressor tryptophan
binds to the trp repressor
protein, and the complex binds
to the operator when
tryptophan levels are high
 High levels of tryptophan
repress the operon
Comparison of
the lac Operon and the trp Operon
Lac
Operon
• It regulates the production of
galactosidase and other proteins
involved in the metabolism of
lacgtose
Trp
Operon
• It regulates the production of the
amino acid tryptophan
Comparison of
the lac Operon and the trp Operon
Lac
Operon
• It consists of a cluster of three
genes under the control of one
promoter and one operator
Trp
Operon
• It consists of a cluster of five
genes under the control of one
promoter and one operator
Comparison of
the lac Operon and the trp Operon
Lac
Operon
• The Lacl repressor protein binds
to the operator when lactose
levels are low
Trp
Operon
• The corepressor tryptophan binds
to the trp repressor protein, and
the complex binds to the operator
when tryptophan levels are high
Comparison of
the lac Operon and the trp Operon
Lac
Operon
• High levels of lactose
induce the operon
Trp
Operon
• High levels of tryptophan
repress the operon
Comparison of
the lac Operon and the trp Operon
lac Operon
trp Operon