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REGULATION OF GENE
EXPRESSION
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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
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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
Changes in the environment and/or food sources
can cause bacteria to switch genes on and off
Gene expression in bacteria is controlled by the
operon model
A.
Feedback Inhibition- inhibits the activity
of the first enzyme in the metabolic
pathway.
A.
Regulation of Gene Expressionenzymes are controlled at the transcription
level, by turning genes on/off.
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A. Operons: The Basic Concept
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1. The operon was discovered in 1961 by Francois Jacob and
Jacques Monod and was proposed as a model for the
control of gene expression in bacteria
2. A cluster of functionally related genes can be under
coordinated control by a single on-off “switch”
3. The regulatory “switch” is a segment of DNA called an
operator usually positioned within the promoter
4. An operon is the entire stretch of DNA that includes the
operator, the promoter, and the genes that they control
5. The operon can be switched off by a protein repressor
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6. The repressor prevents gene transcription by binding to the
operator and blocking RNA polymerase
7. The repressor is the product of a separate regulatory gene
which is usually located away from the operon they control
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8. The repressor can be in an active or inactive form,
depending on the presence of other molecules
9. A corepressor is a molecule that cooperates with a
repressor protein to switch an operon off
B. Repressible and Inducible Operons:
Two Types of Negative Gene Regulation
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1. Repressible Operon
2. Inducible Operon
*Both are examples of negative gene regulation
B. Repressible and Inducible Operons:
Two Types of Negative Gene Regulation
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1. Repressible Operon
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
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
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2. Inducible Operon
An inducible operon is one that is usually off; a molecule
called an inducer inactivates the repressor and turns on
transcription
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
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C. Inducible enzymes usually function in catabolic pathways;
their synthesis is induced by a chemical signal
D. Repressible enzymes usually function in anabolic
pathways; their synthesis is repressed by high levels of the
end product
E. Regulation of the trp and lac operons involves negative
control of genes because operons are switched off by the
active form of the repressor
F. Positive Gene Regulation
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1. Some operons are also subject to positive control through a
stimulatory protein, such as catabolite activator protein
(CAP), an activator of transcription
2. When glucose (a preferred food source of E. coli) is
scarce, CAP is activated by binding with cyclic AMP
3. Activated CAP attaches to the promoter of the lac operon
and increases the affinity of RNA polymerase, thus
accelerating transcription
4. When glucose levels increase, CAP detaches from the lac
operon, and transcription returns to a normal rate
5. CAP helps regulate other operons that encode enzymes
used in catabolic pathways
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Differential Gene
Expression- the
expression of different
genes by cells with the
same genome.
Gene expression typically
refers to actions
occurring in transcription,
but regulation can
happen at other stages in
more complex
organisms.
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Epigenetic Inheritance- inheritance of
traits transmitted by mechanisms not
directly involving the nucleotide sequence.
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Ex: histone acetylation and DNA methylation
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A.
In histone acetylation, acetyl groups are attached to
positively charged lysines in histone tails which loosens
chromatin structure, thereby promoting the initiation of
transcription
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Neutralizes the positive charge on the lysine which
cause histones to not bind to neighboring nucleosomes.
Causes chromatin to form a looser structure.
Deacetylation- removal of acetyl groups
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A.
In histone acetylation, acetyl groups are attached to
positively charged lysines in histone tails which loosens
chromatin structure, thereby promoting the initiation of
transcription
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B. DNA methylation, the addition of methyl groups to
certain bases in DNA, is associated with reduced
transcription in some species and can cause long-term
inactivation of genes in cellular differentiation
Ex: genomic imprinting
Inactive DNA is typically more methylated than
regions that are actively transcribed. Individual
genes are usually more methylated in cells
where they are not expressed
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C. In alternative RNA splicing, different mRNA molecules
are produced from the same primary transcript,
depending on which RNA segments are treated as
exons and which as introns
INSERT FIGURE 18.10
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Genes with the same control elements are
activated by the same chemical signals.
(Not by a common operator, as in
prokaryotes).
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Control Elements- segments of
noncoding DNA that serve as binding sites
for transcription factors (proteins that
regulate transcription).
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Proximal Control Elements (near promoter)
vs. Distal Control Elements called
Enhancers (upstream or downstream of a
gene or within an intron)
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mRNA Degradation- nucleotide sequences
(in UTR) determine how long mRNA remains
intact. By degrading mRNA, expression is
blocked.
Initiation of Translation- by preventing the
attachment of mRNA on ribosomes,
translation is blocked.
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Can occur when regulatory proteins bind to
sequences in UTR, when poly-A tail isn’t sufficient
in length, or when translation initiation factors are
deactivated.
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Chemical modifications to polypeptides to
make them functional.
Transport to target destinations.
Length of time for protein to function in the
cell.
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When cells are marked for destruction, a
protein called ubiquitin is attached to the
protein surface.
Proteosomes- complexes that recognize
ubiquitin and degrade marked proteins.
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Protein coding DNA = 1.5% of human
genome. Very small percent of noncoding DNA codes for genes of
rRNA/tRNA. Significant amount of
genome may be transcribed into
noncoding RNA (ncRNA)
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MicroRNA (miRNA)- bind to complementary mRNA and
degrades or prevents translation.
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RNA Interference- injecting doublestranded RNA molecules into a cell turns
off expression of a gene with the same
sequence as the RNA.
Small Interfering RNA (siRNA)- similar to
miRNA in size and function.
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Cell Division- zygote gives rise to a large
number or identical cells.
Cell Differentiation- become specialized
in structure and function and organize into
tissues and organs.
Morphogenesis- “creation of form”
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Cytoplasmic
Determinantsmaternal substances
in the egg that
influence the course
of development.
(non-homogenous)
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Inductive Signalssignals from other
nearby embryonic cells
that cause a change in
gene expressionsending a cell down a
specific developmental
path.
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Determination- events that lead to the
observable differentiation of a cell.
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D. Oncogenes are cancer-causing genes
Proto-oncogenes are the corresponding normal cellular
genes that are responsible for normal cell growth and
division
Conversion of a proto-oncogene to an oncogene can lead
to abnormal stimulation of the cell cycle
E. Homeotic genes are any of the master regulatory genes
that control placement and spatial organization of body
parts in animals, plants, and fungi by controlling the
developmental fate of groups of cells
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Homeotic Genes- determine pattern formation.
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Embryonic Lethals- mutations with phenotypes causing death at the
embryonic stage.
Maternal Effect Gene- when mutant in mother, results in mutant
phenotype in offspring, regardless of offspring’s own genotype.
Morphogens- establish an
embryo’s axis and
other
features of its form.
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p53 Gene- codes for a transcription factor
that promotes synthesis of cell-cycle
inhibiting proteins.
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Mutation is this gene usually leads to
excessive cell growth and cancer.
Tumor-Suppressor Genes- code for
proteins that help prevent uncontrolled cell
growth.
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1. Explain the concept of an operon and the function of the
operator, repressor, and corepressor
2. Explain the adaptive advantage of grouping bacterial
genes into an operon
3. Explain how repressible and inducible operons differ and
how those differences reflect differences in the pathways
they control
4. Describe 3 other means of gene regulation
5. Define oncogenes, proto-oncogenes, and homeotic genes
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Explain how DNA methylation and histone
acetylation affect transcription of genes.
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Draw a diagram that represents how
Alternative RNA Splicing can code for two
different proteins.
How is a protein targeted for degradation,
and what cellular component is
responsible for degrading it?
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Explain the effect of cytoplasmic
determinants on cells and cell
differentiation.
Describe what is meant by the term
“embryonic lethals”?