Regulation of Gene Expression

REGULATION OF
GENE EXPRESSION
Dr. Abid Ali
Learning Objectives
• 1: Define the term gene expression
• 2: Explain the mechanism of Regulation of gene expression in
prokaryotes
• 3: Explain the mechanism of Regulation of gene expression in
eukaryotes
• 4: Epigenetics
GENE
EXPRESSON
RNA
Regulation of
Gene Expression
Regulation of Gene Expression
in Prokaryotes
Need of Gene Regulation
Nature of nutrients present in medium

suggests regulation of gene expression
To economize by not investing energy

and resources in synthesis of
unnecessary RNAs (mRNA) and protein
when not required.
This type of regulation keeps order
and prevent waste.
Level/Point of Regulation
In prokaryotes the most significant

level of regulation
is at initiation of transcription level.
The basic concept
• Jacob & Monad 1961
• Operon Model in Lactose Metabolism
• The organization of different operons may

Many genes are vary, but generally all of them include a
arranged along the regulator gene (closely or distantly placed),
chromosomes in operator region, promoter site and a
number of structural gene (cistron)
groups of related
genes. These groups
are called gene
clusters.
Organization
of Operon
Cistron
In prokaryotes there are
two main types of regulations
• Inducible Gene Regulation-
Example Lac Operon-Negative Control
• Regulatory proteins often bind to small molecules, which can
make the protein active or inactive by changing its ability to bind
DNA. Some operons are inducible, meaning that they can be
turned on by the presence of a particular small molecule.
• Repressible Gene Regulation-
Example Tryptophan Operon-Positive Control
• Repressors are proteins that turn off or reduce gene expression,
which is reflected by reduced messenger RNA production from
the affected gene. Repressor proteins typically function through
binding and blocking critical DNA sequences in the gene, such as
the promoter where mRNA transcription starts.
Lac Operon in E. coli:
RNA
POLYMERASE
REPRESSER
PROTEIN
Mechanism of regulation of Lac Operon:
• Lac Operon is regulated by the following three
mechanisms:
1. Induction of Lac mRNA transcription (in the presence of
lactose)
2. Repression of Lac mRNA transcription (in the absence of

lactose)
3. Catabolic repression: (In the presence of glucose and

lactose)
Induction of Lac mRNA transcription (In the
presence of lactose):
Repression /Inhibition of Lac mRNA
transcription (In the absence of lactose):
Catabolite repression or positive control (In
the presence of glucose and lactose):
CAP
We will learn how lactose activates the expression of
lactose metabolizing gene through this animation.
Lac operon Video

• The bacterium E.Coli posseses a highly effective lactose metabolism
process. The Lac operon is a single expressible unit of DNA that
encodes three proteins crucial for lactose metabolism.
• If Lactose is not present in the growth media the bacterium does not
waste energy by expressing these proteins. These proteins wil only
produce when lactose is present to be metabolized.
Tryptophan Operon
TRP Operon Videos
UTR
Attenuation in Trp Operon
trp Operon Transcription Under High Levels of Tryptophan
trp Operon Transcription Under Low Levels of Tryptophan
Trp Attenuation Video
Eukaryotic Gene Regulation
Eukaryotic Gene
Regulation
Gene regulation makes cells different
• Gene regulation is how a cell controls which genes, out of the many
genes in its genome, are "turned on" (expressed).
• Thanks to gene regulation, each cell type in your body has a different
set of active genes – despite the fact that almost all the cells of your
body contain the exact same DNA. These different patterns of gene
expression cause your various cell types to have different sets of
proteins, making each cell type uniquely specialized to do its job.
Eukaryotic gene expression
can be regulated at many stages
Basic structure of Eukaryotic DNA
Fig. 1
Fig. 2
Transcription Factors?
https://www.youtube.com/watch?v=2K2Xcd
LKMZo
Transcription Factors?
https://www.youtube.com/watch?v=2K2XcdLKMZo
What is Epigenetics?
https://www.cdc.gov/genomics/disease/epigenetics.htm
https://www.whatisepigenetics.com/fundamentals/
Types of Epigenetic changes are
•DNA methylation,
•Wrapping and unwrapping of
chromatin,
•Histone Acetylation
DNA methylation
• DNA methylation is an
epigenetic mechanism used
by cells to control gene
expression. ... DNA
methylation refers to the
addition of a methyl (CH3)
group to the DNA strand
itself, often to the fifth carbon
atom of a cytosine ring.
• There are two kinds of chromatin
• loosly condensed and
• tightly condensed chromatins.
• There are also pieces of RNA that does
not code.
• You can see your typical mRNA
from a gene that leads to protein
• We also have areas that are non
coding, they don’t code for a
protein. So they actually code small
pieces of RNA called micro RNA.
And micro RNA can base pair with mRNA
so the translation will be prevented. So
one of the way of regulation is using
micro RNA.
Empty boxes are introns
mature RNA
We can cut up the introns and can get smooth RNA.

But it can be different each time, we can end up with a mature RNA
having an extra intron. Now this intron will be considered as exon.
Other ways of Regulation in Eukaryotes
• RNA processing. Splicing, capping, and addition of a poly-A tail to an RNA
molecule can be regulated, and so can exit from the nucleus. Different mRNAs
may be made from the same pre-mRNA by alternative splicing.
• RNA stability. The lifetime of an mRNA molecule in the cytosol affects how many
proteins can be made from it. Small regulatory RNAs called miRNAs can bind to
target mRNAs and cause them to be chopped up.
• Translation. Translation of an mRNA may be increased or inhibited by regulators.
For instance, miRNAs sometimes block translation of their target mRNAs (rather
than causing them to be chopped up).
• Protein activity. Proteins can undergo a variety of modifications, such as being
chopped up or tagged with chemical groups. These modifications can be regulated
and may affect the activity or behavior of the protein.
• Although all stages of gene expression can be regulated, the main control point for
many genes is transcription. Later stages of regulation often refine the gene
expression patterns that are "roughed out" during transcription.
Justify the need for regulation of gene
expression
• The overall idea of gene regulation is efficiency. Even the most minute of
metabolic functions are extremely complex and must be regulated to keep a
balance with everything else that is going on within the cell.
• That being said, one point is that not all genes need to be expressed at one time.
Some gene products, such as proteins, could have antagonistic activities if
present at the same time. Examples of this include anabolic pathways vs.
catabolic pathways. Anabolic pathways are typically being expressed and need to
be turned off, while catabolic ones typically need to be turned on.
Some gene products can be harmful to the cell under certain conditions or if
there is too much of it in the cell. Iron is an example. It is an essential cofactor to
a lot of proteins, such the globular protein of hemoglobin. Yet, it can be a toxin in
that it reacts with oxygen to form free radicals. Free radicals in turn may play a
role in cancer development.
• Supporting the idea of efficiency, cells do not need to make proteins when
they are not needed. Since protein synthesis requires high amounts of
energy, only what is needed is produced. An example involves tryptophan
(trp) production, where tryptophan is needed to make certain proteins.
When high levels of trp are present in the cell, trp acts as something called
a co-repressor, which will bind to a protein that represses the expression of
more trp. When trp levels are low, the repressing protein cannot function
properly, so more trp is produced. This keeps the cell from using more trp
than it has to.
Let it be known that some genes are always turned on. These genes are
called constitutive genes (aka: housekeeping genes). These are genes
whose product is essential to cell metabolism, such as ATP production and
damage repair.
Clinical Applications – Epigenetic Diseases
• Cancer. Cancer was the first human disease to be linked to epigenetics.
• DNA hypomethylation can activate oncogenes and
initiate chromosome instability,
• whereas DNA hypermethylation initiates silencing of tumor suppressor
genes. An accumulation of genetic and epigenetic errors can transform a
normal cell into an invasive or metastatic tumor cell. Additionally, DNA
methylation patterns may cause abnormal expression of cancer-associated
genes.
• Global histone modification patterns are also found to correlate with
cancers such as prostate, breast, and pancreatic cancer.
• Subsequently, epigenetic changes can be used as biomarkers for the
molecular diagnosis of early cancer.
• Mental Retardation Disorders. Epigenetic changes are also linked to several
disorders that result in intellectual disabilities such as ATR-X, Fragile X, Rett,
Beckwith-Weidman (BWS), Prader-Willi and Angelman syndromes.
• Neuropsychiatric Disorders. Epigenetic errors also play a role in the

causation of complex adult psychiatric, autistic, and neurodegenerative
disorders.
• The increased knowledge of epigenetics, combined with rise of

technologies such as CRISPR/Cas9 gene editing and next-generation
sequencing in recent years, allows us to better understand the interplay
between epigenetic change, gene regulation, and human diseases, and
will lead to the development of new approaches for molecular diagnosis
and targeted treatments across the clinical spectrum.
Thank you

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REGULATION OF

Nature of nutrients present in medium

To economize by not investing energy

In prokaryotes the most significant

• The organization of different operons may

2. Repression of Lac mRNA transcription (in the absence of

3. Catabolic repression: (In the presence of glucose and

Lac operon Video

We can cut up the introns and can get smooth RNA.

• Neuropsychiatric Disorders. Epigenetic errors also play a role in the

• The increased knowledge of epigenetics, combined with rise of

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