REGULATION OF GENE EXPRESSION IN PROKARYOTES & EUKARYOTES

To know and explain:
• Regulation of Bacterial Gene Expression
• Constitutive ( house keeping) vs. Controllable genes
• OPERON structure and its role in gene regulation
• Regulation of Eukaryotic Gene Expression at different levels:
• DNA methylation
• Histon modifications(Chromatin Remodeling)
• Increasing the number of gene copies (gene amplification)
• Changing the rate of initiation of transcription
• Alternate splicing
• mRNA stability
• Changing the rate of initiation of translation
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Gene expression is the process by which the information
encoded in a gene is used to direct the assembly of a protein
molecule.
Gene expression is explored through a study of protein structure
and function, transcription and translation, differentiation and
stem cells.
It is the process by which information from a gene is used in the
synthesis of a functional gene product.
These products are often proteins, but in non-protein coding
genes such as ribosomal RNA (rRNA), transfer RNA (tRNA) or
small nuclear RNA (snRNA) genes, the product is a functional
RNA.
The process of gene expression is used by all known life -
eukaryotes (including multicellular organisms), prokaryotes
(bacteria and archaea)
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• Regulation of gene expression includes a wide range of
mechanisms that are used by cells to increase or decrease
the production of specific gene products (protein or RNA).
• Gene regulation is essential for viruses, prokaryotes and
eukaryotes as it increases the versatility and adaptability of
an organism by allowing the cell to express protein when
needed.
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• Although a functional gene product may be an RNA or a
protein, the majority of known mechanisms regulate protein
coding genes.
• Any step of the gene's expression may be modulated, from
DNA-RNA transcription to the post-translational modification
of a protein.
• The first discovered example of a gene regulation system was
the lac operon, discovered by Jacques Monod, in which
protein involved in lactose metabolism are expressed by
E.coli only in the presence of lactose and absence of glucose.
• Gene regulation drives the processes of cellular
differentiation and morphogenesis, leading to the creation of
different cell types in multicellular organisms where the
different types of cells may possess different gene expression
profile.
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Genes are subunits of DNA, the information
database of a cell that is contained inside the cell
nucleus.
This DNA carries the genetic blueprint that is used to
make all the proteins the cell needs.
Every gene contains a particular set of instructions
that code for a specific protein
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Constitutive ( house keeping) genes:
 Are expressed at a fixed rate, irrespective to the cell
condition.
Their structure is simpler.
Controllable genes:
 Are expressed only as needed. Their amount may
increase or decrease with respect to their basal level in
different condition.
Their structure is relatively complicated with some
response elements
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When the expression of genetic information is quantitatively
increased by the presence of specific regulatory element is
known as positive regulation.
Element modulating positive regulation is known as activator or
positive regulator.
When the expression of genetic information is diminished by
the presence of specific regulatory element is known as
negative regulation.
The element or molecule mediating the negative regulation is
said to be repressor.
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Type A response:
Type B response:
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1) RNA polymerase binds to DNA at promoters.
2)Transcription initiation is regulated by proteins
that bind to or near promoters.
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Synthesis of the primary RNA transcript (transcription)
Posttranscriptional modification of mRNA
Messenger RNA degradation
Protein synthesis ( translation )
Posttranslational modification of proteins
Protein targeting & transport
Protein degradation 10/25/2014 14

 In prokaryotes the primary control point is the process of
transcription initiation .
 Different ways for regulation of gene expression in bacteria:
 Regulation of gene expression can be done by some operon
pathways such as
1.lac operon.
2.tryptophan operon.
.
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Transcriptional control
Translational control
Post translational control
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In genetics, an operon is a functioning unit of genomic DNA
containing a cluster of genes under the control of a single
promoter.
Operons occur primarily in prokaryotes but also in some
eukaryotes.
Operons are related to regulons, stimulons and modulons.
An operon is made up of several structural genes arranged
under a common promoter and regulated by a common
operator.
It is defined as a set of adjacent structural genes, plus the
adjacent regulatory signals that affect transcription of the
structural genes.
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An operon is made up of 4 basic DNA components:
Promoter – a nucleotide sequence that enables a gene to be
transcribed. The promoter is recognized by RNA polymerase, which then
initiates transcription.
Regulator – These genes control the operator gene in cooperation
with certain compounds called inducers and corepressors present in the
cytoplasm.
Operator – a segment of DNA that a repressor binds to. It is
classically defined in the lac operon as a segment between the
promoter and the genes of the operon.
Structural genes – the genes that are co-regulated by the
operon.
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Operon regulation can be either negative or positive by induction or
repression.
Negative control involves the binding of a repressor to the
operator to prevent transcription.
In negative inducible operons, a regulatory repressor protein is normally
bound to the operator, which prevents the transcription of the genes on
the operon .
If an inducer molecule is present, it binds to the repressor and changes
its conformation so that it is unable to bind to the operator. This allows
for expression of the operon.
The lac operon is a negatively controlled inducible operon, where the
inducer molecule is allolactose.
In negative repressible operons, transcription of the operon normally
takes place.
The trp operon, involved in the synthesis of tryptophan (which itself acts
as the corepressor ), is a negatively controlled repressible operon.
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With positive control, an activator protein stimulates transcription
by binding to DNA.
In positive inducible operons, activator proteins are normally
unable to bind to the pertinent DNA.
When an inducer is bound by the activator protein, it undergoes a
change in conformation so that it can bind to the DNA and
activate transcription.
In positive repressible operons, the activator proteins are
normally bound to the pertinent DNA segment.
However, when an inhibitor is bound by the activator, it is
prevented from binding the DNA.
This stops activation and transcription of the system.
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• The lac operon of the model bacterium Escherichia coli
was the first operon to be discovered and provides a
typical example of operon function.
• It consists of three adjacent structural genes, a promoter,
a terminator, and an operator.
• The lac operon is regulated by several factors including the
availability of glucose and lactose.
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Discovered in 1953 by Jacques Monod and colleagues, the trp
operon in E. coli was the first repressible operon to be
discovered.
This operon contains five structural genes:
trp E,
trp D,
trp C,
trp B, and
trp A, which encodes tryptophan synthetase.
It also contains a promoter which binds to RNA polymerase and
an operator which blocks transcription when bound to the
protein synthesized by the repressor gene (trp R) that binds to
the operator
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Eukaryotic cells have a much larger genome
Eukaryotes have much greater cell specialization
Thus eukaryotic cells contain an enormous amount of DNA that
does not program the synthesis of RNA or protein
This requires complex organization
In eukaryotes expression of gene into proteins can be
controlled at various locations
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• Synthesis of proteins is controlled right from the chromatin stage.
• Expression of gene is controlled at many steps during the process of
transcription and translation.
• Description of the control points is dealt in detail in the subsequent
slides.
1.Transcriptional control.
2.RNAprocessing control.
3.RNA transport & localisation control.
4.Translation control.
5.mRNAdegradation control.
6.Protein activator control.
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Two forms of chromatin
• Euchromatin – A lesser coiled transcriptionally active region which can
be easily accessed by the RNA polymerases.
• Heterochromatin – A highly condensed transcriptionally inactive region.
The genes in this region cannot be accessed by the RNA polymerases
for active transcription.
• Ubiquitination:
Ubiquitination of H2A – Transcriptional inactivation
Ubiquitination of H2B - Transcriptional activation
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• Histone modifications – These modifications
make a region of gene either transcriptionally
active or inactive.
Acetylation
• ↑Acetylation ----↓ Condensation of DNA ----- ↑
Transcription of genes in that region
Ubiquitination
Ubiquitination of H2A – Transcriptional inactivation
Ubiquitination of H2B - Transcriptional activation
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DNA methylation:is the addition or removal
of a methyl group predominantely where
cytosine bases occur consecutively.
bases occur consecutively.
DNA methylation:is the addition or removal
of a methyl group predominantely where
cytosine bases occur consecutively.
bases occur consecutively.
Methylation occurs most often in
symmetrical CG sequences.
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by HATs and coactivators
leads to euchromatin
formation
by HDACs and
corepressors leads to
heterochromatin formation
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• Eukaryotes – There are two types of promoters which are:
• Basal promoter or core promoter -These promoters reside
within 40bp upstream of the start site. These promoters are seen in all
protein coding genes.
• Upstream promoters - These promoters may lie up to 200bp
upstream of the transcriptional initiation site. The structure of this
promoter and the associated binding factors keeps varying from gene to
gene.
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Transcriptional control:
… controlling when and how often a given gene is
Transcribed
Figure 6. Genes can be expressed with different efficiencies.
Gene A is transcribed and
translated much more efficiently than gene B. This allows the
amount of protein A in the cell to bemuch greater than that of
protein B.
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Enhancers
• Enhancers can be located upstream, downstream or
within the gene that is transcribed
• The binding of these enhancers with enhancer binding
proteins (transcription factors) increases the rate of
transcription of that gene to a greater extent.
• Promoters are capable of initiating lower levels of
transcription.
• Enhancers are responsible for the cell or tissue specific
transcription.
• Each enhancer has its own transcription factor that it
binds to.
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• www.wikipedia.com
• www.slideshare.com
• www.webmed.com
• www.ncbl.com
• Some articles from internet
• Some journals
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REGULATION OF GENE EXPRESSION IN PROKARYOTES & EUKARYOTES

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REGULATION OF GENE EXPRESSION IN PROKARYOTES & EUKARYOTES