UNIT 3: Molecular Genetics
Chapter 7: Genes and Proteins Synthesis
pg. 310 -
7.4: Controlling Gene Expression
pg. 332 - 339
Insulin – is a hormone produced in the pancreas that lowers the blood
glucose level by promoting the uptake of glucose by the body cells.
Prokaryotic Gene Control Mechanisms
The Lac Operon
Lac operon – is a cluster of genes that contains the DNA sequences to
regulate the metabolism of lactose.
Operator – is the region in the operon that regulatory factors bind to.
Repressor protein – is a protein that binds to the operator to repress gene
transcription.
Inducer – is a signal molecule that triggers the expression of an operon’s
gene.
The trp Operon
Corepressor – is a signal molecule that binds to a regulatory protein to
reduce the expression of an operon’s gene.
Eukaryotic Gene Control Mechanisms
The regulation of gene expression in eukaryotes is very complex.
Eukaryotes use a control system consisting of for parts;
Transcriptional (as mRNA is being synthesized)
Post-transcriptional (as mRNA is being processed)
Translational (as the protein is being synthesized)
Post-translational (after the protein has been synthesized)
Transcriptional Regulation
For the gene to be transcribed, the chromatin must be partially unwound to
expose the promoter region.
There are two types of transcriptional regulation:
1. An activator molecule must be bound to a sequence that is upstream to
the gene’s promoter. This signals a protein remodeling complex. The
histone core proteins are displaced from the DNA, exposing the
promoter region.
2. The activator molecule is bound to a regulatory sequence upstream of
the gene. An enzyme adds an acetyl group (CH3COO-) to the histones.
This acetyl groups causes the histones loosen its association with the
DNA molecule and the promoter becomes accessible.
Once the promoter is exposed, a series of proteins (general transcription
factors) accumulate on the promoter along the TATA box. RNA polymerase
is able to bond here and start transcription. Activator and repressor proteins
attach to the promoter region to increase or decrease the rate of transcription.
To inhibit transcription, a Methyl group (-CH3) is added to the cytosine
bases in the promoter region of the gene, this event is called silencing.
Methylation is a way to put genes on hold until they are required.
Figure 4: General transcription factors accumulate on the promoter to initiate transcription.
Post-Transcriptional Regulation
Post-transcriptional regulation is controlled by several mechanisms, such as;
changes in pre-mRNA processing and the rate of mRNAs degrading. The
pre-mRNA (primary transcript) may undergo alternative splicing, producing
different mRNAs by removing different combinations of introns (by
spliceosomes). The remaining exons are spliced together. Depending on the
protein to be synthesized an intron in one protein can be an exon in another.
This allows the cell to optimize the production of different proteins.
Making proteins can be added to mRNAs to make them inactive until
required. This is commonly found in animal eggs, keeping the mRNA
inactive until after the egg has been fertilized.
Another post-transcriptional modification can change the rate of mRNA
degradation. The addition of a 5′ cap and a poly-A-tail is an example of this
type of modification.
*** these regulations (modifications) occur before the mRNA transcript
leaves the Nucleus.
Translation Regulation
Translational regulation occurs during protein synthesis by the ribosome.
Poly-A-tails can be shortened or lengthened on the mRNA, which can
decrease or increase the amount of time it takes for translation to occur.
Post-Translational Regulation
Once the protein has been synthesized, it can still be regulated by limiting
the availability to function. There are three methods for controlling the
functionality of a protein.
The initial protein produced is in an inactive form, controlled by processing
mechanisms. (Insulin is produced in an inactive form called proinsulin)
Processing mechanisms can remove specific section of the protein making
them active.
Chemical modifications of a protein, addition or deletion of chemical groups
from a protein, affects its functionality. These functional groups can put the
protein on hold until it is required b the cell.
Proteins can also be degraded continuously inside and outside the cell. The
rate of degradation is under regulatory control, which can modify the rate of
availability. Ubiquitin is one tag which can control the functional life of a
protein. Degraded proteins are broken down into heir individual amino acids
which are recycled to synthesized new proteins.
Table 1: Four levels of Control of Gene Expression in Eukaryotic Cells
Transcriptional: it regulates which genes are translated (DNA to mRNA)
or controls the rate at which transcription occurs.
Posttranscriptional: the mRNA molecules undergo changes in the nucleus
before translation occurs. Introns are removed and exons
are spliced together.
Translational:
it controls how often and how rapidly mRNA transcripts
will be translated into proteins. This control affects the
length of time it takes for mRNA to be activated and the
speed at which cytoplasmic enzymes destroy mRNA.
Posttranslational: before many proteins become functional, they must pass
through the cell membrane. A number of control
mechanisms affect the rate at which a protein becomes
active and the time it remains functional, including the
addition of various chemical groups.
Cancer
Cancer cells do not have the regulatory mechanisms. Cancer cells
continually add telomeric sequences, which allow cancer cells to grow out of
control. This is controlled by gene expressions which may have been
mutated.
The exposure to mutagens has an accumulative affect over time on possible
mutations. As the cell accumulates mutations, cellular functions are affected.
Mutations in one cell can only be passed on to its daughter cells during cell
division.
Changes in gene regulation are caused by mutations in the promoter and
coding regions that affect the function of a protein. Viruses may also deliver
foreign DNA to the cell which affected protein function.