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AP Biology 12
Regulation of Prokaryote and Eukaryote Genomes (Chapter 18)
How does this all fit together???
Big Idea 2: Biological systems utilize free energy and molecular building blocks to grow, to
reproduce and to maintain dynamic homeostasis.
Essential knowledge
Chapters/sections
2.e.1 Timing and
coordination of specific
events are necessary for the
normal development of an
organism, and these events
are regulated by a variety of
mechanisms.
18.2, 18.3, 18.4
38.1
Illustrative examples
covered
• Morphogenesis of fingers
and toes
• Immune function
• C. elegans development
• Flower Development
Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life
processes.
3.B.1 Gene
18.1, 18.2, 18.3
• Promoters
regulation results in
• Terminators
differential gene
• Enhancers
expression, leading to
cell specialization.
3.B.2 A variety of intercellular
and intracellular signal
transmissions mediate gene
expression.
11.1, 11.4
18.1, 18.2, 18.3, 18.4
• Cytokines regulate gene expression to allow
for cell replication and division
• Mating pheromones in yeast trigger mating
gene expression
• Levels of cAMP regulate metabolic gene
expression in bacteria
• Expression of the SRY gene triggers the male
sexual development pathway in animals
• Ethylene levels cause changes in the
production of different enzymes, allowing
fruits to ripen
• Seed germination and gibberellin
• Mating pheromones in yeast trigger mating
genes expression and sexual reproduction
• Morphogens stimulate cell differentiation and
development
• Changes in p53 activity can result in cancer
• HOX genes and their role in development
Big Idea 4: Biological systems
interact, and these systems and
their interactions possess
complex properties.
4.A.3: Interactions between
external stimuli and
regulated gene expression result in
specialization of cells, tissues and
organs.
18.4
No illustrative examples listed in the
Curriculum Framework.
Cell Processes and Applications – Gene Regulation (Chapter 18)
 Describe similarities and differences between prokaryotic and eukaryotic genomes
 Describe some mechanisms by which gene expression is regulated in prokaryotes and
eukaryotes
 Describe cancer with respect to:
 abnormal nuclei
 disorganized and uncontrolled growth (anaplasia)
 lack of contact inhibition
 vascularization
 metastasis
 List the seven danger signals that may indicate the presence of cancer (handout/notes)
 Differentiate between a proto-oncogene and an oncogene
 Use examples to outline the roles of initiators and promoters in carcinogenesis
(handouts/notes)
 Demonstrate a knowledge of how a virus can bring about carcinogenesis
Overview: Conducting the Genetic Orchestra
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Both prokaryotes and eukaryotes alter their patterns of gene expression in response to
changes in environmental conditions.
In multicellular eukaryotes, each cell type contains the same genome but expresses a different
subset of genes.
During development, gene expression must be carefully regulated to ensure that the right
genes are expressed only at the correct time and in the correct place.
Gene expression in eukaryotes and bacteria is often regulated at the transcription stage.
○ Control of other levels of gene expression is also important.
RNA molecules play many roles in regulating eukaryotic gene expressions.
Disruptions in gene regulation can lead to cancer.
MP3 Tutor: Control of Gene Expression chapter 18 website
D8: Describe some mechanisms by which gene expression is regulated in prokaryotes (and
eukaryotes.)
How do prokaryotes
control their metabolic
pathways? For example,
how do they control the
metabolic pathway that
synthesizes the amino acid
tryptophan?
 Natural selection
favors bacteria that
express only those
genes whose
products are needed
by the cell.
○ A bacterium in a
tryptophan-rich
environment that
stops producing
tryptophan
conserves its
resources.
 Metabolic control occurs on two levels.
 First, cells can adjust the activity of enzymes already present.
○ This may happen by feedback inhibition, in which the activity of the first
enzyme in a pathway is inhibited by the pathway’s end product.
○ Feedback inhibition, typical of anabolic (biosynthetic) pathways, allows
a cell to adapt to short-term fluctuations in the supply of a needed
substance.
 Second, cells can vary the number of specific enzyme molecules they make
by regulating gene expression.
○ Genes of the bacterial genome may be switched on or off by changes in
the metabolic status of the cell.
Describe how bacteria use a repressible operon to ‘turn the tap’ on and off a metabolic
pathway that is producing a molecule that the cell requires – for example, tryptophan.
http://bcs.whfreeman.com/thelifewire/content/chp13/1302002.html
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A cluster of functionally related genes can be under coordinated control by a
single on-off “switch”
The regulatory “switch” is a segment of DNA called an operator usually
positioned within the promoter. That means that the oerator controls
transcription.
An operon is the entire stretch of DNA that includes the operator, the promoter,
and the genes that they control
• The operon can be switched off by a protein repressor
• The repressor prevents gene transcription by binding to the operator
and blocking RNA polymerase
• The repressor is the product of a separate regulatory gene
• The repressor can be in an active or inactive form, depending on the
presence of other molecules
• A corepressor is a molecule that cooperates with a repressor protein
to switch an operon off
• For example, E. coli can synthesize the amino acid tryptophan
• 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
Repressible and Inducible Operons: Two Types of Negative Gene Regulation
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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
An inducible operon is one that is usually off; a molecule called an inducer
inactivates the repressor and turns on transcription
Describe how bacteria use inducible operons to turn on metabolic pathways when a
particular metabolite is present. (See Activity: The lac Operon in E. coli)
• 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
•
• Inducible enzymes usually function in catabolic pathways; their synthesis is
induced by a chemical signal
• Repressible enzymes usually function in anabolic pathways; their synthesis is
repressed by high levels of the end product
• Regulation of the trp and lac operons involves negative control of genes
because operons are switched off by the active form of the repressor
Describe how bacteria ‘fine tune’ the control of the lac operon, depending on whether
glucose is present or absent – positive gene regulation
See Lac operon animations:
http://www.dartmouth.edu/~cbbc/courses/movies/LacOperon.html does not work on
chrome
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Some operons are also subject to positive control through a stimulatory protein,
such as catabolite activator protein (CAP), an activator of transcription
When glucose (a preferred food source of E. coli) is scarce, CAP is activated by
binding with cyclic AMP
Activated CAP attaches to the promoter of the lac operon and increases the
affinity of RNA polymerase, thus accelerating transcription
When glucose levels increase, CAP detaches from the lac operon, and
transcription returns to a normal rate
CAP helps regulate other operons that encode enzymes used in catabolic
pathways
The Regulation of Eukaryotic Gene Expression
Ref:18.2
Here is a photo of a salamander egg (a eukaryotic cell) in interphase. You can see that some parts
are ‘unwound’ as the genes in this region are being expressed:
A major concept in cell differentiation in multicellular eukaryotes is ‘differential gene
expression’. What is meant by this?
• In multicellular organisms gene expression is essential for cell specialization
• To perform it’s role each gene must maintain a specific program of gene
expression in which certain genes are expressed and others are not.
• A human cell expresses about 20% of it’s genes at any one time. The more
highly differentiated the cells are the smaller the fraction of genes expressed.
D8: Describe some mechanisms by which gene expression is regulated in (prokaryotes and)
eukaryotes. (Cell differentiation involves differential gene expression)
18_PPTLecture\1621DNAPacking_A.swf
Note: only about 20% of the genome of
a typical human cell is being expressed
at any one time. In a human, only about
1.5% of the DNA codes for protein.
Eukaryotic Control of Gene Expression
(see web activity in chapter 18)
__also page 356
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The DNA of eukaryotic cells is packaged
with proteins in a complex called
chromatin.
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Genes within highly packed
heterochromatin are usually not expressed
presumably because transcription proteins
cannot reach the DNA.
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Chemical modifications of the histones
and DNA of chromatin play a key role
in chromatin structure and gene
expression.

The N-terminus of each histone
molecule in a nucleosome protrudes
outward from the nucleosome.
○
These histone tails are accessible to
various modifying enzymes, which
catalyze the addition or removal of
specific chemical groups.
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Histone acetylation (addition of an acetyl
group, —COCH3) and deacetylation appear
to play a direct role in the regulation of
gene transcription.
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Acetylated histones grip neighboring
nucleosomes less tightly, providing easier
access for transcription proteins in this
region.
Several other chemical groups, such as methyl and phosphate groups, can be reversibly attached
to amino acids in histone tails.
○
The attachment of methyl groups (—CH3) to histone tails leads to condensation of
chromatin. DNA methylation reduces gene expression.
○
The addition of a phosphate group (phosphorylation) to an amino acid next to a methylated
amino acid has the opposite effect.
This diagram is from chapter 16 and it shows how the DNA in eukaryotes is packed using
various histone proteins. The corresponding electron micrographs of the DNA at the various
stages is also shown.
Some interesting facts about the human genome:
The total number of genes in the human genome is about 25,000.
Each chromosome has about 1.5 X 108 nucleotide pairs (average) and is about 4 cm long if
stretched out. The total DNA from both parents is about 2 meters per cell if stretched out.
How does it fit into the cell, along with the other 45 chromosomes?
What is the difference between heterochromatin and euchromatin?
Euchromatin is the less condensed form of eukaryotic chromatin that is available for
transcription.
Heterochromatin is eukaryotic chromatin that remains highly compacted during
interphase and is generally not transcribed.
In what form is the chromatin during interphase?
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Although the chromatin modifications just discussed do not alter DNA sequence,
they may be passed to future generations of cells
The inheritance of traits transmitted by mechanisms not directly involving the
nucleotide sequence is called epigenetic inheritance
a) Regulation of Chromatin Structure - Control of DNA packing and unpacking:
How are ‘methylation’ and ‘acetylation’ involved in the packing and unpacking of chromatin?

Histone acetylation (addition of an acetyl group, —COCH3) and deacetylation appear to play a direct
role in the regulation of gene transcription.

Acetylated histones grip neighboring nucleosomes less tightly, providing easier access for transcription
proteins in this region.
○
Some of the enzymes responsible for acetylation or deacetylation are associated with or are
components of transcription factors that bind to promoters.
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Thus, histone acetylation enzymes may promote the initiation of transcription not only by modifying
chromatin structure but also by binding to and recruiting components of the transcription machinery.

Several other chemical groups, such as methyl and phosphate groups, can be reversibly attached to amino
acids in histone tails.
○
The attachment of methyl groups (—CH3) to histone tails leads to condensation of chromatin.
○
The addition of a phosphate group (phosphorylation) to an amino acid next to a methylated amino
acid has the opposite effect.
How does the eukaryote cell control the transcription of specific genes?
Activity: Control of Transcription
The control of transcription in eukaryotes depends on the binding of activators
to DNA control elements.
Explain why liver cells transcribe the albumin gene (a blood protein) and not the crystalline gene
(main protein of the lens), whereas lens cells express the crystalline gene and not the albumin
gene.
Refer to fig. 18.1 page 361

The specific transcription factors.
All activators required for high level expression of the
albumin gene are only present in liver cells and high
level expression of the crystalline gene are only present
in lens cells
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Multiple control elements are associated with most
eukaryotic genes.
○
Control elements are noncoding DNA
segments that regulate transcription by binding
certain proteins.
○
These control elements and the proteins they
bind are critical to the precise regulation of
gene expression in different cell types.
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Activators can bind to enhancers and influence the promoter region of a gene thousands of
nucleotides away. Several protein transcription factors must be present in order for RNA
polymerase to transcribe the gene:
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How does the eukaryotic cell turn on all the genes needed for a particular metabolic pathway at
the same time? (co-ordinately controlled genes)
Control elements for the various genes are all activated together, even though the genes are
widely spaced throughout the genome.
○
Coordinate gene expression in eukaryotes depends on the association of a specific control
element or combination of control elements with every gene of a dispersed group.
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A common group of transcription factors binds to all the genes in the group, promoting
simultaneous gene transcription.
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For example, a steroid hormone enters a cell and binds to a specific receptor protein in the
cytoplasm or nucleus, forming a hormone–receptor complex that serves as a transcription
activator.
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Other signal molecules control gene expression indirectly by triggering signal-transduction
pathways that lead to activation of transcription.
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Every gene whose transcription is stimulated by that steroid hormone has a control element
recognized by that hormone–receptor complex.
The principle of coordinate regulation is the same: Genes with the same control elements are
activated by the same chemical signals.
Systems for coordinating gene regulation probably arose early in evolutionary history and evolved
by the duplication and distribution of control elements within the genome.
A Eukaryotic Gene and Its Transcript
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Post-transcriptional control of gene expression may involve alternative methods of RNA
processing: Activity on Mastering Biology: Post transcriptional control mechanisms
RNA Processing page 362 READ
Alternative RNA splicing. Page 363 Figure 18.13
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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.
○
Regulatory proteins specific to a cell type control intron-exon choices by binding to
regulatory sequences within the primary transcript.
○
Alternative RNA splicing significantly expands the repertoire of a set of genes.
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The life span of an mRNA molecule is an important factor in determining the pattern of protein
synthesis. Animation mRNA degradation on hard drive

Prokaryotic mRNA molecules are typically degraded after only a few minutes.

Eukaryotic mRNAs typically last for hours, days, or weeks.
○
In red blood cells, mRNAs for hemoglobin polypeptides are unusually stable and are
translated repeatedly.
Post-transcriptional control may involve passage of the mRNA molecule through the nuclear
envelope , mRNA degradation, control of translation of the mRNA, protein modification, or
protein degradation by a proteasome:
Animation: Blocking Translation (on hard drive)
Refer to Fig 18.15 page 365
This diagram shows how translation of an mRNA molecule can be blocked by the presence of
another type of RNA (miRNA) microRNAs: This is a type of translational control. As well, it
shows how mRNA can be degraded, which is another type of post-translational control of gene
expression.
SiRNA, small interfering RNAs, have the same effect.
Animation: Protein Processing – hard drive
Animation: Protein Degradation hard drive
Cell Differentiation in Multicellular Organisms
What are some of the factors
within the cell that lead to
differential gene expression and
ultimately cell specialization in
multicellular organisms?
Cytoplasmic materials are distributed unevenly in the unfertilized egg
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Animation: Cell Signaling
In cell specialization, determination is followed by differentiation:
Muscle cells develop from embryonic precursors that have the potential to develop into a number of
alternative cell types, including cartilage cells, fat cells, or multinucleate muscle cells.
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Particular conditions commit certain embryonic precursors to become muscle cells.
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Although the committed cells are unchanged, they are now myoblasts.
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Eventually, the myoblasts begin to synthesize muscle-specific proteins and fuse to form mature,
elongated, multinucleate skeletal muscle cells.
○
Researchers isolated different genes by causing each to be expressed in a separate embryonic
precursor cell and then looking for differentiation into myoblasts and muscle cells.
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They identified several “master regulatory genes” that, when transcribed and translated, commit the
cells to become skeletal muscle.
One of these master regulatory genes is called myoD.
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myoD encodes MyoD protein, a transcription factor that binds to specific control elements in the
enhancers of various target genes and stimulates their expression.
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Some target genes for MyoD encode for other muscle-specific transcription factors.
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MyoD also stimulates expression of the myoD gene itself, perpetuating its effect in maintaining the cell’s
differentiated state.
This diagram illustrates some of the stages in the development of the Drosophila larva, an
organism that has been highly studied:
(on evolution video Great transformations)
Scientists studied mutations in Drosophila in
order to understand the molecular basis of
pattern formation, which is the development of
a spatial organization in which the tissues and
organs are in their characteristic places. Early
studies of this type were carried out by Edward
Lewis. He discovered the homeotic genes.
Much further work on developmental genes was carried out by Nǖsslein-Volhard and Wieschaus
about 30 years later. Many of their experiments involved maternal effect genes (also called egg
polarity genes) that are responsible for setting up the cytoplasmic determinants in the egg. Here
is one example experiment:
18.5 Cancer results from genetic changes that affect the cell cycle: (not for exam)
What is a proto-oncogene?
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Identify 3 ways that a proto-oncogene can be modified and thereby lead to cancer:
Page 374
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Oncogene proteins and faulty tumor-suppressor proteins interfere with normal signalling
pathways:
Multiple mutations underlie the development of cancer (carcinogenesis):