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11
Regulation of Gene
Expression
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
Gene expression is tightly regulated.
Gene expression may be modified to counteract environmental
changes, or gene expression may change to alter function in the
cell.
Constitutive proteins are actively expressed all the time.
Inducible genes are expressed only when their proteins are
needed by the cell. It is based on a feedback mechanism
• Negative regulation—a repressor protein prevents transcription
• Positive regulation—an activator protein binds to stimulate
transcription
Figure 11.1 Potential Points for the Regulation of Gene Expression
Points of Potential Regulation of
Genes
Transcription
Processing of mRNA
Translation
Post-translational
Gene Expression is precisely regulated
Gene Expression is precisely regulated
Maintain stable conditions -hormones
To perform cellular functions, keratin in skin, hemoglobin in
RBC’s
Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after
Transcription
Three ways to regulate mRNA translation:
• Inhibition of translation with miRNAs
• Modification of the 5′ cap end of mRNA can be
modified—if cap is unmodified mRNA is not
translated.
• Repressor proteins can block translation directly—
translational repressors
Concept 11.4 Eukaryotic Gene Expression Can Be Regulated after
Transcription
MicroRNAs(miRNAs)—small molecules of noncoding
RNA—are regulators of gene expression. example
In C. elegans, soil worm, lin-14 mutations cause the
larvae to skip the first
lin-4 mutations cause cells to repeat stage one events—
thus the normal role for lin-4 is to negatively regulate
lin-14, so that cells can progress to the next stage of
development.
lin-4 codes for miRNA that inhibits lin-14 expression
posttranscriptionally by binding to its mRNA.
once miRNAs’ transcribed they are guided to a target
mRNA to inhibit its translation and to degrade the
mRNA.
Figure 11.17 mRNA Degradation Caused by MicroRNAs
Figure 11.18 A Repressor of Translation
Protein Stability can be Regulated
Proteins can be targeted for
destruction
Begins when an enzyme attaches to a
76 amino acid protein called Ubiquitin
(it is ubiquitous in cells)
More ubiquitins attach to form a
polyubiquitin chain
This then binds to a proteasome, a
protein complex which contains
enzymes.
The polyubiquitin is removed and ATP
is used to unfold the protein. It is
digested into peptides and amino
acids. Cyclins in the cell cycle are
regulated in this way.
Figure 11.2 Positive and Negative Regulation
General Operon Model
Gene expression begins at the
Promoter where RNA
Polymerase binds to initiate
transcription
A gene cluster with a single
promoter is an operon
An operator is a short stretch
of DNA near the promoter that
controls transcription of the
structural genes.
Two types of regulatory
proteins—transcription
factors—control whether a
gene is active.
Repressors are
Negative
Activators are Positive,
AKA Inducers
Example of gene control
Prokaryotes conserve energy by making proteins only
when needed.
In a rapidly changing environment, the most efficient
gene regulation is at the level of transcription.
E. coli must adapt quickly to food supply changes in
Glucose or lactose.
Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons
Generally, inducible (positive) systems control catabolic
pathways—turned on when substrate is available
Repressible systems (negative) control anabolic
pathways—turned on until product becomes
excessive
Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons
Lac Operon encodes for the lactose enzymes
Lac Operon is an Inducible operon (Positive)—turned off
unless needed
If lactose is present and glucose is low, E. coli synthesizes
enzymes.
If lactose is absent, synthesis stops.
A compound that induces protein synthesis (transcription)
is an inducer.
Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons
Uptake and metabolism of lactose by E. coli involve
three proteins:
• -galactoside permease—a carrier protein that moves
sugar into the cell
• -galactosidase—an enzyme that hydrolyses lactose
• -galactoside transacetylase—transfers acetyl groups
to certain -galactosides
If E. coli is grown with no lactose present, no enzymes
for lactose conversion are produced.
Lac Operon Inducible Gene operon Model Active Repressor-no Transcription
Gene
region
Gene Activation Inactivate Repressor Transcription takes place
Concept 11.2 Many Prokaryotic Genes Are Regulated in Operons
The lac operon is only transcribed when a -galactoside
predominates in the cell:
• In the presence of a -galactoside, the repressor
detaches and allows RNA polymerase to initiate
transcription.
• A repressor protein is normally bound to the operator,
which blocks transcription.
The key to this regulatory system is the repressor
protein.
Repressor Gene Trp Operon
A repressible operon is switched off when its repressor
is bound to its operator.
However, the repressor only binds in the presence of a
co-repressor.
The co-repressor causes the repressor to change shape
in order to bind to the promoter and inhibit
transcription.
Tryptophan functions as its own co-repressor, binding to
the repressor of the trp operon.
Figure 11.9 The trp Operon: A Repressible System Catalysis of Amino Acid Tryptophan
Figure 11.9 The trp Operon: A Repressible System
Figure 11.6 Two Ways to Regulate a Metabolic Pathway
To Summaryize
Difference in two types of operons:
In inducible systems—a metabolic substrate (inducer)
interacts with a regulatory protein (repressor); the
repressor cannot bind and allows transcription.
In repressible systems—a metabolic product (corepressor) binds to regulatory protein, which then
binds to the operator and blocks transcription.
Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors
and DNA Changes
Transcription factors act at eukaryotic promoters.
Each promoter contains a core promoter sequence
where RNA polymerase binds.
TATA box is a common core promoter sequence—rich in
A-T base pairs.
Only after general transcription factors (TF) bind to the
core promoter, can RNA polymerase II bind and
initiate transcription.
Figure 11.10 The Initiation of Transcription in Eukaryotes
Concept 11.3 Eukaryotic Genes Are Regulated by Transcription Factors
and DNA Changes
Transcription factors recognize particular nucleotide
sequences:
NFATs (nuclear factors of activated T cells) are
transcription factors that control genes in the immune
system.
They bind to a recognition sequence near the genes’
promoters.
The binding produces an induced fit—the protein
changes conformation.
Viral Regulation of Genes
Viruses are non-living entities which become activated
when they have infected a host cell
They can contain DNA or RNA as their genetic material
They have a protein coat to protect the genetic material
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
Acellular viruses use gene regulation to take over host
cells.
A bacteriophage will infect bacteria
A phage injects a host cell with nucleic acid that takes
over synthesis.
New viral particles (virions) appear rapidly and are soon
released from the lysed cell.
This lytic cycle is a typical viral reproductive cycle
lysogenic cycle, the viral genome is incorporated into
the host genome (prophage DNA) and is replicated
too. However, something will trigger this to occur.
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
The lytic cycle has two stages:
• Early stage—promoter in the viral genome binds
host RNA polymerase and adjacent viral genes are
transcribed
Early genes shut down transcription of host genes,
and stimulate viral replication and transcription of
viral late genes.
Host genes are shut down by a posttranscriptional
mechanism.
Viral nucleases digest the host’s chromosome for
synthesis in new viral particles.
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
• Late stage—viral late genes are transcribed
They encode the viral capsid proteins and enzymes to
lyse the host cell and release new virions.
The whole process from binding and infection to release
of new particles takes about 30 minutes.
Figure 11.3 A Gene Regulation Strategy for Viral Reproduction
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
Human immunodeficiency virus (HIV) is a retrovirus
with single-stranded RNA. It infects white blood cells.
HIV is enclosed in a membrane from the previous host
cell—it fuses with the new host cell’s membrane.
After infection, RNA-directed DNA synthesis is catalyzed
by reverse transcriptase.
Two strands of DNA are synthesized and reside in the
host’s chromosome as a provirus.
Concept 11.1 Several Strategies Are Used to Regulate Gene Expression
Host cells have systems to repress the invading viral
genes.
One system uses transcription “terminator” proteins
that interfere with RNA polymerase.
HIV counteracts this negative regulation with Tat
(Transactivator of transcription), which allows RNA
polymerase to transcribe the viral genome.
Figure 11.4 The Reproductive Cycle of HIV
Figure 11.5 Regulation of Transcription by HIV
Table 11.1 Transcription in Bacteria and Eukaryotes