Gene Regulation Is Necessary
 ~42 000 genes exist that code for proteins in humans,
but not all proteins are required
 By switching genes off when they are not needed, cells
can prevent resources from being wasted.
 The ability to switch genes on an off is naturally
selected
 A typical human cell normally expresses about 3% to
5% of its genes at any given time.
 Cancer results from genes that do not turn off properly.
Cancer cells have lost their ability to regulate mitosis,
resulting in uncontrolled cell division.
 Gene expression in eukaryotes is controlled by a
variety of mechanisms that range from those that
prevent transcription to those that prevent expression
after the protein has been produced.
 The various mechanisms can be placed into one of
these four categories: transcriptional,
posttranscriptional, translational, and
posttranslational.
 Transcriptional
 prevent mRNA from being synthesized
 Ex: Barr bodies in females are inactive because tightly
wound
 Post-transcriptional
 Regulate mRNA after it is produced
 Ex: a single mRNA can code for 3 proteins, depending on
which introns are removed
 Translational
 Prevent protein synthesis
 Proteins may bind to regions of the mRNA strand
preventing the ribosomes from translating it.
 Post-translational
 Prevent the protein from becoming functional
 Ex: Proteins are often not fully functional after
translation. Proinsulin is a precursor to insulin. It needs
to be cut into 2 polypeptide chains and have 30 amino
acids removed.
Prokaryotes
 Much of our understanding of gene control comes
from studies of prokaryotes.
 Prokaryotes have two levels of gene control.
Transcriptional and translational.
Operons
 Operons are groups of genes that function to produce
proteins needed by the cell.
 Prokaryotic cells use operons to regulate genes and
their respective proteins.
Operons are made up of:
 Structural Genes – code for the proteins needed.
 Ex: the proteins needed to breakdown sugar
 Promoter – are where RNA polymerase binds to the
DNA
 (Lots of A-T base pairs!)
 Operator – a short sequence of bases between
structural genes and a promoter.
The lac operon
 Lactose is a sugar found in milk.
 If lactose is present, E. coli (the common intestinal
bacterium) needs to produce the necessary enzymes to
digest it.
 Three different enzymes are needed.
 In the diagram genes A, B, and C represent the genes
whose products are necessary to digest lactose.
 In the normal condition, the genes do not function
because a repressor protein is active and bound to
the DNA preventing transcription.
 When the repressor protein is bound to the DNA, RNA
polymerase cannot bind to the DNA.
 The protein must be removed before the genes can be
transcribed.
Lac operon – with repressor (no
transcription)
Below: Lactose binds with the
repressor protein inactivating it.
Transcription!
Lac operon
 The lac operon is an example of an inducible operon
because the structural genes are normally inactive.
They are activated when lactose is present.
The trp operon
 Repressible operons are the opposite of inducible
operons.
 Transcription occurs continuously and the repressor
protein must be activated to stop transcription.
 Tryptophan is an amino acid needed by E. coli and the
genes that code for proteins that produce tryptophan
are continuously transcribed as shown below.
 However, if tryptophan is present in the environment,
E. coli does not need to synthesize it and the
tryptophan-synthesizing genes should be turned off.
 This occurs when tryptophan binds with the repressor
protein, activating it.
 Unlike the repressor discussed with the lac operon,
this repressor will not bind to the DNA unless it is
activated by binding with tryptophan. Tryptophan is
therefore a co-repressor.
 The trp operon is an example of a repressible operon
because the structural genes are active and are
inactivated when tryptophan is present.
Negative and Positive Control
 The trp and lac operons discussed above are examples
of negative control because a repressor blocks
transcription.
 In one case (lac operon) the repressor is active and
prevents transcription.
 In the other case (trp) the repressor is inactive and
must be activated to prevent transcription.
 Positive control mechanisms require the presence of
an activator protein before RNA polymerase will
attach.
 The activator protein itself must be bound to an
inducer molecule before it attaches to mRNA.
Genes which code for enzymes
necessary for the digestion of
maltose are regulated by this
mechanism. Maltose acts as
the inducer, binding to an
activator and then to DNA. The
activator bound to DNA
stimulates the binding of RNA
polymerase.
Methylation
 The attachment of a methyl group to histone proteins
can promote or inhibit transcription (by either causing
the DNA to unravel from the nucleosome or stay
tightly bonded to the nucleosome).
 If the methyl group is attached directly to DNA,
transcription will be inhibited because RNA
polymerase cannot attach.
Methylation of Cytosine
Methylation of a Nucleosome
Methylation
 The amount of DNA methylation varies during a
lifetime and is affected by environmental factors.
 Identical twins will have identical DNA but will have
different levels of methylation because they have
different experiences.
 Differences in the expressed genes is why identical
twins may not look or act exactly the same.
Epigenetics
 Epigenetics is the study of cellular and physiological traits
that are NOT caused by changes in the DNA sequence.
 This done via chemical modifications (such as methylation,
phosphorylation, or acetylation) and are called epigenetic
tags.
 Scientific evidence shows that not only does the
environment effect the expression of genes, but that
epigenetic factors may be heritable (passed on to the next
generation).
 Different cells have their
own methylation pattern
so that a unique set of
proteins will be
produced in order for
that cell to perform its
function.
 During cell division, the methylation pattern will be
passed over to the daughter cell.
 In other words, the environment is affecting
inheritance.
 Sperm and eggs develop from cells with epigenetic
tags.
 When a sperm and egg cell meet to form a zygote, the
epigenome (the sum of all the epigenetic tags) are
removed through a process called “reprogramming”.
 About 1% of the epigenome is not erased and is passed
on to the next generation. This is called “imprinting”.
 Ex: A pregnant mother may develop gestational
diabetes (temporary diabetes while she is pregnant).
 As a result, high levels of glucose in the fetus can
trigger epigenetic changes to the fetus’ DNA giving the
child an increased chance of developing diabetes itself.
 Data Base Question:
 Changes in Methylation
Pattern with age in
Identical Twins
 One study compared the methylation patterns of 3-year
olds identical twins with 50 year old identical twins
 Methylation patterns were dyed red on one chromosome
for own twin and dyed grene for the other twin on the same
chromsomes.
 The result would be a yellow colour if the patterns were the
same.
 Differences in patterns on the two chromosomes result in
green and red patches.
 This was done for 4 pairs of chromsomes.
1.
Explain the reason for
the yellow colouration
if the methylation
pattern is the same in
the 2 twins.
2. Identify the
chromosome with the
least changes as the
twins age.
3. Identify the chromosomes
with the most changes as the
twins age.
4. Explain how these
differences could arise
5. Predict with a reason
whether identical twins will
become more or less similar
to each other in their
characteristics as they grow
older.