Cell Biology Gene Expression and Regulation

Cell Biology: Gene Expression and Regulation
The cell is often referred to as the building blocks of life. This is
because it is the smallest unit and the most fundamental in the
structural, functional and biological unit of all living organisms.
Cells replicate independently to form new ones. The human body is
estimated to consist of approximately 100 trillion cells. Each cell has
46 chromosomes with identical DNA sequences. However, cells do not
express the DNA they contain the same way. Whilst a certain DNA sequence
may be ‘turned on’ in one cell, the same DNA sequence may be present
in another but a ‘turned off’ state. There is a mechanism that
regulates gene expression.
Mechanisms involved in gene regulation
Gene regulation refers to the wide range of mechanisms that cells employ
to modulate gene expression. The objective is to determine which genes
will be switched off or on, when and for how long, and also the extent
to which genes will be expressed. This regulation may occur anytime
within the stages of gene expression.
#1 Transcriptional Regulation
Transcription is the initial step in gene expression. During
transcription, a precise segment of the DNA is copied into the RNA by an
enzyme known as RNA polymerase (Morris, 2008). Gene regulation during
transcription involves controlling when transcription occurs and at the
same time monitoring how much RNA is created. There are a number of
factors that can be used to regulate genes at this stage (Morris, 2008):
Repressors- they bind themselves on the DNA strand that are close to the
promoter area. This impedes RNA polymerase’s progress along that
strand. By so doing, expression of the gene has been obstructed.
Specificity factors- these factors alter specificity of RNA polymerase
for a promoter or a set of promoters. This reduces or increases the
chances of a DNA strand being copied to that RNA.
Activators- they encourage gene expression by enhancing the interaction
between RNA polymerase and a definite promoter. This is made possible
through increasing a promoter’s attraction to RNA polymerase.
Enhancers- these are sites on the DNA helix on which activators are
bound. They cause the DNA to loop, bringing a definite promoter to the
initiation complex.
Silencers- these are similar to enhancers but work conversely to them.
Silencers are sites on which transcription factors are bound that
obstruct gene expression for a definite promoter.
General transcription factor- they position RNA polymerase at the
beginning of the protein-coding sequence. After that, they release the
enzyme to transcribe the mRNA.
#2 Post-transcriptional regulation
This is control of gene expression at the RNA level. After the DNA
subscription that results in the formation of mRNA, regulation is
required to determine how much of the mRNA will be translated into
proteins. Cells do so by capping modulation, splicing, adding a Poly (A)
tail, and sometimes sequestrating the RNA transcript (Morris, 2008).
Translational regulation
This involves regulation of the levels of protein synthesized by the
mRNA. Modulation here can involve elongation or termination of protein
synthesis or recruitment of ribosomes (Francois & Monod, 1961).
mRNA degradation
Different mRNA within the same cell have different lifetimes. The amount
of protein that can be synthesized from a mRNA depends on the length of
its stability. This limited mRNA lifetime presents an opportunity to
control protein synthesis. Cells alter protein synthesis rapidly
according to the changing needs (Francois & Monod, 1961).
Different gene expression in different cell types
There are numerous genes in a cell, but only a fraction of them are
expressed at a time. Cells are able to change the genes they express
without altering the nucleotide sequence of their DNA. The choices, as
well as expression revolve around determination and differentiation.
Determination involves choosing the definite gene a cell wants to
express. Differentiation follows as the cell manifests the developmental
program of its choice that involves expressing the chosen genes.
This means that differentiation is a product of differential gene
expression. Different cells end up having different sets of proteins by
expressing a definite set of genes. Differentiation results in the
formation of cells whose identity and function are clear-cut such as the
skin cells, muscle cells, and nerve cells. Cells of an organism differ
not because their genetic composition is different, but because they
express them differently.
Most of the cells in multicellular organisms have the ability to alter
their gene expression patterns in response to external signals. For
example, if a liver cell is exposed to a steroid such a glucocorticoid
hormone, the cells will trigger an increase in the production of precise
proteins. One such protein is tyrosine aminotransferase that assists in
conversion of tyrosine to glucose. A fat cell reacts to the presence of
glucocorticoid hormone differently. In fact, fat cells lower the
production of tyrosine aminotransferase when exposed to the
glucocorticoid hormone.
Gene regulation is a complex affair in eukaryotes compared to
prokaryotes. One of the reasons is that eukaryotes have a greater number
of regulatory proteins than prokaryotes. Secondly, due to the large size
of eukaryotes, the binding sites may be located far from transcriptional
promoter sites. Thirdly, eukaryotic gene expression is regulated by a
combination of a number of regulatory proteins. All these factors allow
for flexibility in the control of gene expression.
Beckwith-Wiedemann syndrome
This condition results from abnormal gene regulation in the short arm of
chromosome 11. It is an overgrowth syndrome which if expressed at birth
means that infants become larger than normal. Throughout childhood, the
victims continue to gain weight and grow at an unusual rate. Some of the
body parts grow unusually large which results in asymmetric appearance
(Judd, 2010). At about eight years of age, growth begins to slow down.
Ultimately, adults who suffered this syndrome do not show any unusual
tallness.
Most people born with this syndrome are born with an opening in the
abdominal wall that leaves abdominal organs protruding through the
navel. Other symptoms include a protruding belly-button, an abnormally
large tongue, large abdominal organs, pits in the skin near the ears,
hypoglycemia at infancy and kidney problems. Children with this
condition are highly predisposed to cancerous and noncancerous tumors
(Judd, 2010). Despite the scary symptoms, statistics show that only one
out of five children born with this condition die from complications
related to the disorder. As they grow up, the chances of suffering any
serious medical problem associated with the disorder become low.
Effect of the genetic disease
Molecular level- every person inherits one copy of chromosome 11 from
each parent. In most cases, both copies of the inherited genes are
turned on in cells. For some genes, either the copy inherited from the
father, or the one inherited from the mother is expressed. This
phenomenon where gene expression differences are parent-specific is
called genomic imprinting. Beckwith-Wiedemann Syndrome is one of the
abnormalities involving genes on chromosome 11 that have undergone
genomic imprinting.
Half of the reported cases result from methylation. Methylation is a
chemical reaction that causes small molecules known, as methyl to be
attached to definite segments of the DNA. Beckwith-Wiedemann Syndrome
results from changes in DNA sites on chromosome 11. These sites are
known as imprinting control regions (ICRs). ICRs regulate methylation of
a number of genes that support normal growth such as H19, IGF2 and
CDKN1C. If methylation does not happen usually, these genes are
disrupted. Such an interruption causes an overgrowth in body parts, and
also other symptoms that characterize this syndrome.
Cellular level- A genetic change known as uniparental disomy (UPD) is
responsible for 10-20% of deaths as a result of Beckwith-Wiedemann
Syndrome. Paternal UPD causes victims to have dual active copies of
paternally expressed imprinted genes instead of one. This happens early
in the embryonic development stage affecting some of the body cells.
This phenomenon called mosaicism leads to an imbalance between the
active paternal and maternal genes on chromosome 11.
Organismal level- These imbalances are manifested by individuals
suffering from Beckwith-Wiedemann Syndrome as symptoms. Parents who have
one child suffering from Beckwith-Wiedemann Syndrome are at risk of
getting other children with the same condition. However, the risk
depends on the genetic cause of the condition. While some abnormalities
are inherited from parents, others occur randomly during the formation
of the eggs and sperms or in the earliest child development phase (Judd,
2010). This condition affects 1 out of every 12000 newborns worldwide.
References
Francois, J. & Monod, J. (1961). Genetic Regulatory Mechanisms in the
Synthesis of Proteins. Journal of Molecular Biology vol 3(3), 318-356.
http://www.sciencedirect.com/science/article/pii/S0022283661800727
Judd, S. J. (2010). Genetic disorders sourcebook: Basic consumer health
information about heritable disorders, including disorders resulting
from abnormalities in specific genes. Detroit, MI: Omnigraphics.
Morris, K. V. (2008). RNA and the regulation of gene expression: A
hidden layer of complexity. Norfolk: Caister Academic Press.
CELL BIOLOGY PAGE * MERGEFORMAT 8
CELL BIOLOGY

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