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Chapter 10
Gene Control
Albia Dugger • Miami Dade College
10.1 Between You and Eternity
• Cancer is a multistep process in which cells grow and divide
abnormally, disrupting physical and metabolic functions
• More than 200,000 new cases of breast cancer are diagnosed
in the US each year – about 5,700 in women and men under
thirty-four years of age
• Mutations in genes that control cell growth and division
predispose individuals to develop certain kinds of cancer
normal cells in organized clusters
disorganized clusters of malignant cells
Figure 10-1b p163
10.2 Switching Genes Off and On
• All body cells contain the same DNA with the same genes
• Gene controls govern the kinds and amounts of substances in
a cell at any given time
• Various control processes regulate all steps between gene
and gene product
Cell Differentiation
• Differentiation
• The process by which cells become specialized
• In multicelled organisms, most cells differentiate when
they start expressing a unique subset of their genes
• Which genes are expressed depends on the type of
organism, its stage of development, and environmental
conditions
Gene Controls
• Control over which genes are expressed at a particular time is
crucial for proper development
• Gene controls start, enhance, slow, or stop the individual
steps of gene expression
• Gene controls can operate at any step in the path of protein
production
DNA
new RNA
transcript
mRNA
Nucleus
1 Transcription
Binding of transcription factors to
special sequences in DNA slows or
speeds transcription. Chemical
modifications and chromosome
duplications affect RNA polymerase’s
physical access to genes.
2 mRNA Processing
New mRNA cannot leave the nucleus
before being modified, so controls over
mRNA processing affect the timing of
transcription. Controls over alternative
splicing influence the final form of the
protein.
3 mRNA Transport
RNA cannot pass through a nuclear pore
unless bound to certain proteins.
Transport protein binding affects where
the transcript will be delivered in the cell.
Cytoplasm
mRNA
4 Translation
An mRNA’s stability influences how
long it is translated. Proteins that
attach to ribosomes or initiation factors
can inhibit translation. Double-stranded
RNA triggers degradation of
polypeptide complementary mRNA.
chain
5 Protein Processing
A new protein molecule may become
activated or disabled by enzymemediated modifications, such as
phosphorylation or cleavage. Controls
active
over these enzymes influence many
protein
other cell activities.
Stepped Art
Figure 10-2 p164
ANIMATED FIGURE: Controls of eukaryotic
gene expression
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Control of Transcription
• Transcription factors
• Regulatory proteins that affect the rate of transcription by
binding to special nucleotide sequences in DNA
• Activators speed up transcription when bound to a
promoter; or may bind to distant enhancers
• Repressors slow or stop transcription
Control of Transcription (cont.)
• Chromatin structure also affects transcription
• Chemical modifications and chromosome duplications affect
RNA polymerase’s access to genes
• Enzymes that acetylate histones encourage transcription
• Adding a methyl group to a histone prevent transcription
• Polytene chromosomes (many copies) increase
transcription rates in some organisms
Drosophila Polytene Chromosomes
Controls of mRNA Transcripts
• mRNA processing
• DNA splicing controls products of translation
• mRNA transport controls delivery of transcripts
• Passage through nuclear pores
• Delivery within cytoplasm (mRNA localization)
Translational Controls
• Controls over mRNA stability
• Depends on base sequence, length of poly-A tail, and
which proteins are attached to it
• RNA interference
• Expression of a microRNA complementary to a gene
inhibits expression of the gene
Post-Translational Modification
• Post-translational modification can inhibit, activate, or stabilize
many molecules, including enzymes that participate in
transcription and translocation
Take-Home Message:
What is gene control?
• Gene controls consist of molecules and structures that can
start, enhance, slow, or stop individual steps of gene
expression
• Most cells of multicelled organisms differentiate as they start
expressing a unique subset of their genes; which genes a
cell expresses depends on the type of organism, its stage of
development, and environmental conditions
10.3 Master Genes
• Cascades of gene expression govern the development of a
complex, multicelled body
• Master genes encode products that affect the expression of
many other genes
• Pattern formation is the process by which a complex body
forms from local processes in an embryo
Pattern Formation
• As an embryo develops, cells that differentiate in different
body regions migrate and form tissues, creating complex
body forms from local processes driven by master genes
• Regional gene expression during development results in a 3dimesional map that consists of overlapping concentrations of
master gene products, which change over time
Gene Expression Control in a Fly
Homeotic Genes
• Homeotic genes
• Master genes that control differentiation of specific tissues
and body parts in an embryo
• Encode transcription factors with a homeodomain
• Homeodomain
• A region of about 60 amino acids that can bind to a
promoter or some other sequence in DNA
A Homeodomain
Knockout Experiments
• Knockout experiments
• Researchers inactivate a gene by introducing a mutation
into it, then compare the differences with normal
individuals – and similar genes in humans
• Example: The PAX6 gene in humans is a homologue of the
eyeless gene in Drosophila
Eyeless
PAX6
Take-Home Message:
How do genes control development?
• Development is orchestrated by cascades of master gene
expression in embryos
• The expression of homeotic genes during development
governs the formation of specific body parts; homeotic genes
that function in similar ways across taxa are evidence of
shared ancestry
10.4 Examples of
Gene Control in Eukaryotes
• Selective gene expression gives rise to many traits
X Chromosome Inactivation
• X chromosome inactivation
• In cells of female mammals, either the maternal or
paternal X chromosome is randomly condensed (Barr
body) and is inactive
• Occurs in an early embryonic stage, so that all
descendents of that particular cell have the same inactive
X chromosome, resulting in “mosaic” gene expression
Inactivated X Chromosomes
Mosaic Tissues in a Human Female
Dosage Compensation
• Dosage compensation
• The theory that X chromosome inactivation equalizes
expression of X chromosome genes between the sexes
• Mechanism of X inactivation
• XIST gene on one X chromosome transcribes an RNA
molecule which coats the chromosome and causes it to
condense, forming a Barr body
Male Sex Determination in Humans
• Most of the 1,336 genes on the X chromosome determine
nonsexual traits such as blood clotting and color perception
• The human Y chromosome carries 307 genes, including SRY
– the master gene that triggers formation of testes in males
• Testosterone produced by the testes causes formation of
male genitalia and secondary sexual traits
• In the absence of testosterone, female genitalia form
Structures that will give rise
to external genitalia appear
at seven weeks
SRY expressed
no SRY present
penis
vaginal
opening
birth approaching
Figure 10-8 p168
Flower Formation
• The ABC model
• Three sets of master genes (A,B,C) encode products that
initiate cascades of expression of other genes to
accomplish intricate tasks such as flower formation
• Master genes are expressed differently in tissues of floral
shoots
• Master genes are switched on by environmental cues
such as day length
petals
sepals
carpel
stamens
A The pattern in which the
floral identity genes A, B,
and C are expressed
affects differentiation of
cells growing in whorls in
the plant’s tips. Their gene
products guide expression
of other genes in cells of
each whorl; a flower results.
Figure 10-9a p168
Figure 10-9b p168
ANIMATED FIGURE: ABC model for
flowering
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Take-Home Message: What are some
examples of gene control in eukaryotes?
• X chromosome inactivation balances expression of X
chromosome genes between female (XX) and male (XY)
mammals
• SRY gene expression triggers the development of male traits
in mammals
• In plants, expression of ABC master genes governs
development of the specialized parts of a flower
ANIMATION: X-chromosome inactivation
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10.5 Gene Control in Prokaryotes
• Prokaryotes (bacteria and archaea) are single celled and do
not have master genes
• Prokaryotes control gene expression mainly by adjusting the
rate of transcription in response to shifts in nutrient availability
and other outside conditions
Prokaryotic Gene Control
• In prokaryotes, genes that are used together often occur
together on chromosomes
• Operon
• A promoter and one or more operators that collectively
control transcription of multiple genes
• Operators
• DNA regions that are binding sites for a repressor
The Lac Operon
• E. coli digest lactose in guts of mammals using a set of three
enzymes controlled by two operators and a single promoter
(the lac operon)
• When lactose is not present, repressors bind to the operators
and inactivate the promoter; transcription does not proceed
• When lactose is present, allolactose binds to the repressors;
repressors don’t bind to operators to inactivate the promoter;
transcription proceeds
1 The lac operon in the E. coli chromosome.
Lactose absent
2 In the absence of lactose, a repressor binds to the two
Repressor protein
operators. Binding prevents RNA polymerase from attaching
to the promoter, so transcription of the operon genes does
not occur.
Lactose present
lactose
3 When lactose is present, some is converted to a form that
binds to the repressor. Binding alters the shape of the
repressor such that it releases the operators. RNA
polymerase can now attach to the promoter
and transcribe the operon genes.
Stepped Art
Figure 10-10 p170
ANIMATED FIGURE: The lactose operon
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repressor
looped-up
DNA
looped-up
DNA
Figure 10-11 p171
Lactose Intolerance
• Human infants and other mammals produce the enzyme
lactase, which digests the lactose in milk
• Humans begin to lose the ability to produce lactase, around
age 5, and become lactose intolerant
• Many people of European ancestry carry a mutation in one of
the genes responsible for programmed lactase shutdown
Riboswitches
• Some bacterial mRNAs regulate their own translation with
riboswitches – small sequences of RNA nucleotides that bind
to a target molecule
• Binding of an end product (such as vitamin B12) changes the
shape of the mRNA so that ribosomes no longer attach to it,
and translation stops – an example of feedback inhibition
Take-Home Message:
Do bacteria control gene expression?
• In bacteria, the main gene expression controls regulate gene
expression in response to shifts in nutrient availability and
other environmental conditions
• Prokaryotes can regulate gene expression using operons and
riboswitches
10.6 Epigenetics
• Methylations and other modifications that accumulate in DNA
during an individual’s lifetime can be passed to offspring
DNA Methylations
• Direct methylation of DNA suppresses gene expression in a
more permanent manner than histone modification
• Example: The active X chromosome in cells of female
mammals does not express the XIST gene because its
promoter is heavily methylated
• Cancer is often associated with the loss of methylation, which
suppresses the activity of transposable elements
DNA Methylations
• Between 3 and 6 percent of DNA in body cells is methylated
• Methyl groups often attach to a cytosine followed by a
guanine, but which cytosines are methylated varies by
individual
• In some cases, a decrease in methylations that results in an
increase in expression of a gene may offer a survival
advantage
DNA Methylation
• Methylation of cytosine
followed by a guanine
DNA Methylation
• Methyl groups attached
to cytosine-guanine
pairs on complementary
DNA strands
Heritable Methylations
• Once a base in a cell’s DNA becomes methylated, it usually
stays methylated in all of the cell’s descendants
• Methylation patterns in parental chromosomes are normally
“reset” in the first cell of the new individual, with new methyl
groups being added and old ones being removed
• However, not all parental methyl groups are removed, so
methylations acquired during an individual’s lifetime can be
passed to future offspring
Epigenetic Inheritance
• Any heritable changes in gene expression that are not due to
changes in DNA sequence are said to be epigenetic
• Epigenetic inheritance can adapt offspring to environmental
stressors much more quickly than evolutionary processes
• Epigenetic marks may persist for generations after an
environmental stressor has faded
• Effects are sex-limited: boys are affected by lifestyle of male
ancestors; girls, by individuals in the maternal line
Examples of Epigenetic Inheritance
• Grandsons of boys who endured a winter of famine when they
were 6 years old lived about 32 years longer than the
grandsons of boys who overate at the same age
• Nine-year-old boys whose fathers smoked cigarettes before
age 11 are very overweight compared with boys whose
fathers did not smoke in childhood
A Cause of Epigenetic Changes
• 1944 famine in Nazioccupied Netherlands
• Grandsons of survivors
had extended lifespans
Take-Home Message:
Can gene expression be inherited?
• Epigenetic marks in chromosomal DNA, including DNA
methylations acquired during an individual’s lifetime, can be
passed to offspring