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Control of Gene Expression
Gene Regulation Is Necessary
~ 42 000 genes exist that code for proteins in humans, but not all proteins are required
at all times.
By switching genes off when they are not needed, cells can prevent resources from
being wasted. There should be natural selection favouring the ability to switch genes on
and off.
A typical human cell normally expresses about 3% to 5% of its genes at any given time.
Housekeeping genes are genes that are switched on all the time because they are
needed for vital functions
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.
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:
1. Structural Genes – code for the proteins needed. Ex: the proteins needed to
breakdown sugar
2. Promoter – are where RNA polymerase binds to the DNA
3. Operator – a short sequence of bases between structural genes and a promoter.
Note: the promoter and operator regions have a small area of overlap
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 diagrams below, lacZ, lacY and lacA represent the genes whose products
are necessary to digest lactose. In the normal condition, the genes do not function
because a repressor protein (LacI) 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.
When lactose is present, it binds directly to the LacI protein and therefore
“removes the roadblock”. For this reason, lactose is known as a signal molecule or
inducer. Transcription of the three genes can now proceed.
a) When lactose is not present in the cell environment, the LacI protein binds to the lac
operator, covering part of the promoter and thereby, blocking transcription
b) Lactose binds to the LacI protein, changing its shape. It can no longer bind to the lac
operator and transcription proceeds
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 for the production of protein and
the genes that code for proteins that produce tryptophan are continuously transcribed
as shown below. E. coli bacteria are capable of making their own tryptophan. If there
is a high concentration of tryptophan present in the intestinal environment, the E. coli
no longer needs to produce their own, and transcription is stopped.
This operon contains five different genes that code for five polypeptides that
make three enzymes. These three enzymes are needed to synthesize tryptophan. Since
tryptophan and the active repressor are both needed to inactivate the trp operon,
tryptophan is called a corepressor.
a) Lack of tryptophan inactivates the repressor and transcription proceeds
b) Tryptophan acts as a corepressor and binds to the tryptophan repressor. The
complex can now bind to the trp operator and transcription is blocked
The trp operon is an example of a repressible operon because the structural
genes are active and are inactivated when tryptophan is present.