Controlling Gene Expression
Gene expression in prokaryotes and eukaryotes is regulated in response to the cellular
life cycles and environmental conditions. The optimal functioning of an organism requires that
genes be turned on and off as they are needed. Intricate sstems have evolved to fine-tune the
expression of genes in both prokaryotes and eukaryotes.
Housekeeping genes: code for proteins that are always needed in a cell. These genes are
continuously transcribed and translated. These genes regulate the processes of metabolism,
growth and DNA replicaiotn and transcription.
Prokaryotes: Lac and trp Operons
In prokaryotes, gene expression is regulated in response to the concentrations of lactose and
tryptophan. Both responses are examples of negative feedback control.
The Lac Operon
The Lac operon is a cluster of three genes that code for the proteins involved in the metabolism of
lactose.
There are three key regions of the operon itself (promoter, operator and genes for metabolizing
proteins) and there is a gene for a lac repressor immediately upstream from the lac operon.
The gene for the lac repressor (LacI) is continuously transcribed and is always present in the
cell. It takes cues from the environment of the cell (concentration of lactose).
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If lactose is absent, the repressor remains bound to the operator (controls the
transcription of the genes for the metabolizing proteins) and transcription is blocked.
In the presence of lactose, the lactose binds to the repressor changing its shape and
making it inactive. In this state, the repressor can no longer bind to the operator and
the metabolizing proteins are made.
Lactose itself acts as a signal molecule telling the cell when to synthesize the lactose
metabolizing proteins. This makes lactose an inducer because it serves to initiate the
production of the enzymes.
The trp Operon
Tryptophan is an important amino acid that prokaryotes can either make or take up from the
environment. The trp operon tells the cell if it has to make its own tryptophan. The trp operon
has the same structure of the lac operon but the activity of the repressor is different. In the lac
operon the presence of the lactose caused the repressor to be released, in the trp operon, the
presence of tryptophan causes the repressor to bind to the operon.
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When tryptophan is absent, the repressor gene is in the inactive state and does not bind
to the operator and tryptophan is synthesized by the cell.
When tryptophan is present, it binds to the repressor and changes the shape so that it
can bind to the operator region of the operon.
In the trp operon, tryptophan acts as a corepressor because binding of tryptophan to the
repressor allows the repressor to bind to the operator.
Eukaryotes
Gene expression in eukaryotes is more complex because protein synthesis occurs in more than
one step. Eukaryotes do not use the operon system as prokaryotes do, rather there are four
different categories of gene expression mechanisms in eukaryotes.
Transcriptional regulation
DNA organization: because the DNA is wrapped around histones, not all the promoter regions
are accessible for the proteins that initiate transcription. Inorder to unwrap from the histones,
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activator molecules may bind to the DNA exposing the promoter region, or
repressor molecules may bind to the DNA to conceal the promoter or to stop
transcription.
Methylation (a methyl group is added to the cytosine bases in the promoter region of a gene
inhibiting transcription) through a process called silencing
Post-transcriptional Regulation:
Alternative Splicing: produces different mRNAs from pre mRNA by removing different
combinations of introns. For each member of a protein family, introns and exons are different.
This method is used to optimize the production of different proteins depending on the cell
type.
Masking proteins: keep mRNAs in an inactive form until it is time for that mRNA to be
translated. This is common in animal eggs that have the mRNA ready in case of fertilization.
Hormones are a regulatory molecule that will directly or indirectly affect the rate of
degradation of a particular mRNA…
Translational Regulation:
Changing the length of the poly-A tail: adding or removing extra A bases may increase or
decrease the time required for the translation of the protein.
Post-Translational Regulation:
Processing: proteins exist in the cell in precursor forms and processing mechanisms remove
particular sections of the protein and activate it. Ex: Preinsulin
Chemical modification: certain chemical groups are added to or removed from a protein
affecting its function. The presence or absence of the chemical groups puts the protein on hold
until it is needed.
Degradation: proteins with short life spans are marked with ubiquitin. This is recognized by the
degradation mechanisms of the cell. By adding and removing these markers, the lifespan of the
cell can be either shortened or extended.