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Faculty of Chemical and Food Engineering

MSc. Program of Industrial Biotechnology Technology

Assignment for the course Molecular Biology


(ChEg 6181) On
Regulation of Gene Expression

Name: Girma Gishe

ID No.: BDU1500393

Date: Febraury, 2023

Bahir Dar,1 Ethiopia


Introduction

 For a cell to function properly, necessary proteins must be


synthesized at the proper time. All cells control or
regulate the synthesis of proteins from information
encoded in their DNA. The process of “turning on” a gene
to produce mRNA and protein is called gene expression.
 In a simple unicellular organism or a complex multi-cellular
organism, each cell controls when its genes are expressed, how
much of the protein is made, and when it is time to stop
making that protein because it is no longer needed. The control
of gene expression is extremely complex. Malfunctions in this
process are detrimental to the cell and can lead to the
development of many diseases.
1. Prokaryotic versus Eukaryotic Gene

Expression
Since prokaryotic organisms are single-celled organisms that
lack a cell nucleus, their DNA floats freely in the cell’s
cytoplasm. When a particular protein is needed, the gene that
codes for it is transcribed in mRNA, which is simultaneously
translated into protein. When the protein is no longer needed,
transcription stops. As a result, the primary method to control
how much of each protein is expressed in a prokaryotic cell
is the regulation of transcription.
Eukaryotic cells, in contrast, have intracellular organelles that add
to their complexity. In eukaryotic cells, the DNA is contained
inside the cell’s nucleus, where it is transcribed into mRNA.

The newly synthesized mRNA is then modified and transported


out of the nucleus into the cytoplasm, where ribosomes translate
the mRNA into protein. The processes of transcription and
translation are physically separated by the nuclear membrane;
transcription occurs only within the nucleus, and translation occurs
only in the cytoplasm .
 The organism to adapt to its environment and
to conserve energy and nutrients, the
expression of genetic information must be cued
to extrinsic signals and respond only when
necessary.
Some differences in the regulation of gene expression
between prokaryotes and eukaryotes
1.1 Prokaryotic Gene Regulation

 The DNA of prokaryotes is organized into a


circular chromosome that resides in the
cell’s cytoplasm. Proteins that are needed
for a specific function, or that are involved
in the same biochemical pathway, are
often encoded together in blocks called
operons.
Operon

 For example, all five of the genes needed to


make the amino acid tryptophan in the
bacterium E. coli are located next to each other
in the trp operon. The genes in an operon are
transcribed into a single mRNA molecule. This
allows the genes to be controlled as a unit: either
all are expressed, or none is expressed.
 Each operon needs only one regulatory region,
including a promoter, where RNA polymerase
binds, and an operator, where other regulatory
proteins bind. In prokaryotic cells, there are
three types of regulatory molecules that can
affect the expression of operons. Activators are
proteins that increase the transcription of a gene.
 Repressors are proteins that suppress
transcription of a gene. Finally, inducers
are molecules that bind to repressors and
inactivate them.
 The following two examples show how
these molecules regulate different operons.
1.2.The trp Operon: A Repressor Operon

Like all cells, bacteria need amino acids to survive.


Tryptophan is one amino acid that the bacterium E. coli
can either ingest from the environment or synthesize.
When E. coli needs to synthesize tryptophan, it must
express a set of five proteins that are encoded by five
genes.
 However, when tryptophan availability is low,
the trp operon is turned on so that the genes are
transcribed, the proteins are made, and
tryptophan can be synthesized
1.3.The lac Operon: An Inducer Operon

 The lac operon in E. coli has more complex regulation,


involving both a repressor and an activator. E. coli uses
glucose for food, but is able to use other sugars, such as
lactose, when glucose concentrations are low.

 Three proteins are needed to break down lactose; they are


encoded by the three genes of the lac operon. When
lactose is not present, the proteins to digest lactose are
not needed
 lac Z: β Galactosidase
 lac Y: Permease
 lac A:Thiogalactoside transacetylase
Now the bacterium needs to ramp up production of
the lactose-digesting proteins. It does so by using
an activator protein called catabolite activator
protein (CAP). When glucose levels drop, cyclic
AMP (cAMP) begins to accumulate in the cell.
cAMP binds to CAP and the complex ramps up
transcription of the genes.
 For the lac operon to be fully activated, two conditions must
be met. First, the level of glucose must be very low or non-
existent. Second, lactose must be present. Only when glucose
is absent and lactose is present will the lac operon be
transcribed maximally.
2. Eukaryotic Gene Regulation

 In eukaryotes, control of gene expression is more


complex and can happen at many different levels.
Eukaryotic genes are not organized into operons, so
each gene must be regulated independently.
 In eukaryotic regulation of gene expression can
happen at any of the stages as DNA is transcribed
into mRNA and mRNA is translated into protein.
For
convenience, regulation is divided into five levels:
epigenetic, transcriptional, post-transcriptional,
translational, and post-translational
2.1. Epigenetic Control for Gene Expression

 Epigenetic control involves changes to genes that do


not alter the nucleotide sequence of the DNA and are
not permanent.

Instead, these changes alter the chromosomal structure


so that genes can be turned on or off..
One example of chemical modifications of DNA is the
addition of methyl groups to the DNA, in a process called
methylation. in general, methylation suppresses
transcription.

The best studied example of epigenetic regulation is


modification of histone proteins. Histones are
chromosomal proteins that tightly wind DNA so that it fits
into the nucleus of a cell.
 In each chromosome, DNA is wound around histone
proteins to pack it into the nucleus of a cell. The first
level of organization, or packing, is the winding of
DNA strands around histone proteins. Histones
package and order DNA into structural units called
nucleosome complexes, which can control the access
of proteins to the DNA regions as shown on the figure.
DNA is wrapped around histones to create nucleosomes (a), which
control the access of proteins to DNA. When viewed through an
electron microscope (b), the nucleosomes look like beads on a
string.

 If a gene is to be transcribed, the nucleosomes surrounding that


region of DNA can slide down the DNA to open that specific
chromosomal region and allow access for RNA polymerase and
other proteins, called transcription factors, to bind to the
promoter region and initiate transcription.
2.2.Transcriptional Control of Gene Expression

 Transcriptional regulation is control of whether or not an


mRNA is transcribed from a gene in a particular cell. Like
prokaryotic cells, the transcription of genes in eukaryotes
requires an RNA polymerase to bind to a promoter to initiate
transcription.
 In eukaryotes, RNA polymerase requires other proteins, or
transcription factors, to facilitate transcription initiation.
Transcription factors are proteins that bind to the promoter
sequence and other regulatory sequences to control the
transcription of the target gene. RNA polymerase by itself
cannot initiate transcription in eukaryotic cells.

 Transcription factors must bind to the promoter region first and


recruit RNA polymerase to the site for transcription to begin.
Enhancers and Repressors

 In some eukaryotic genes, there are regions that help increase


transcription. These regions, called enhancer.

 Like prokaryotic cells, eukaryotic cells also have mechanisms


to prevent transcription. Transcriptional repressors can bind to
promoter or enhancer regions and block transcription.
2.3 Post-transcriptional Control of Gene
Expression

 Post-transcriptional regulation occurs after the


mRNA is transcribed but before translation
begins. This regulation can occur at the level of
mRNA processing, transport from the nucleus to
the cytoplasm, or binding to ribosomes
Alternative RNA splicing

 In eukaryotic cells the RNA primary transcript


often contains introns, which are removed prior
to translation. Alternative RNA splicing is a
mechanism that allows different combinations
of introns, and sometimes exons, to be
removed from the primary transcript
Control of RNA Stability

 Another type of post-transcriptional control


involves the stability of the mRNA in the
cytoplasm. Many factors contribute to mRNA
stability, including the length of its poly-A tail.
3.4. Translational Control of Gene Expression

 After an mRNA has been transported to the


cytoplasm, it is translated into proteins. Control
of this process is largely dependent on the mRNA
molecule. Translation can also be regulated at the
level of binding of the mRNA to the ribosome .
3.5.Post-translational Control of Gene Expression

 The final level of control of gene expression in


eukaryotes is post-translational regulation. This
type of control involves modifying the protein
after it is made, in such a way as to affect its
activity. One example of post-translational
regulation is enzyme inhibition.
THANK YOU!

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