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GENE EXPRESSION
AND REGULATION

PRESENTED BY
CHINCHU RAVI
M PHARM 1st YEAR
DPS, CHERUVANDOOR
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GENE
• 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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GENE EXPRESSION
• Gene expression refers to the multistep process that
ultimately results in the production of functional gene
product, either RNA or DNA.
• Organism adapt to environmental changes by altering
gene expression.
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REGULATION OF GENE EXPRESSION

• The regulation of gene expression is necessary for the growth ,

development , differentiation , and the existence of the
organism.
• It include wide range of mechanism that are used by cell to
increase or decrease the production of specific gene product.
• Gene regulation is essential for viruses , prokaryotes and
eukaryotes as it increase the versatility and adaptability of an
organism by allowing the cell to express protein when
needed
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TYPES OF GENE
CONTROLLABLE GENE
• Expressed only as needed
• Their amount may increase or decrease with respect to their
basal level in different condition.

CONSTITUTIVE GENE
•The product of the genes are required all the time in a cell
•These are expressed at more or less constant rate in almost
all the cells
•They are not subjected to regulation.
Eg. Enzymes of citric acid cycle
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CONSTITUTIVE GENES
•The product of the genes are required all the time in a cell
•These are expressed at more or less constant rate in almost all
the cells
•They are not subjected to regulation.
Eg. Enzymes of citric acid cycle
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TYPES OF GENE EXPRESSION AND REGULATION

Positive regulation
• When the expression of genetic information is quantitatively
increased by the presence of specific regulatory element.
• Element modulating positive regulation is known as activator
or positive regulator.

Negative regulation
• When the expression of genetic information is decreased by
the presence of a specific regulatory element.
• The element or molecule mediating the negative regulation is
said to be repressor.
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GENE EXPRESSION AND

REGULATION : PROKARYOTES
OPERON
Operon is the coordinated unit of genetic expression.
It consist of
Structural gene
Operator gene
Regulator gene
Promotor site
Lac operon
Tryptophan operon
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Lac – operon
The concept was based on lactose metabolism in E-coli

It consist of
• Structural gene: It carries three structural gene Z,Y and A
• Z gene encodes β galactosidase - which hydrolyses
lactose to galactose and glucose

• Y gene produce permease-transport of lactose and

galactose

• A gene codes for thiogalactoside transacetylase

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Operator gene or O gene :

It is located on the upstream side of the Z gene.

Regulator or i gene :
Transcribe mRNA which codes for repressor protein
Promotor site :
Enzyme RNA polymerase binds and it makes structural genes
Z,Y and A

• Transcription of gene start from promoter located near to

Z gene

• RNA polymerase binds to promoter-transcribe 3 structural

genes as single mRNA
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Repression of Lac operon

• Regulator gene (I gene) is a constitutive gene and it is
independent of inducer
• It is expressed at constant rate leading to the synthesis of
subunits Lac repressor
• Repressor protein molecule has high affinity for operator
gene.
• It is bind to the operator gene.
• This binding prevent the binding of RNA polymerase to the
promotor site.
• Preventing the transcription of structural gene.
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Derepression of Lac operon

• Lactose promote derepression and induction of Lac operon
• Inducer molecule react with the repressor molecule
• Inactivation of repressor molecule
• DNA dependent RNApolymerase attached to the DNA at the
promoter site and permeates to operator locus and
transcription of structural gene.
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TRYPTOPHAN OPERON
• The trp operon is an operon—a group of genes that are used, or
transcribed, together—that codes for the components for
production of tryptophan

• The trp operon is present in many bacteria, but was first

characterized in Escherichia coli

• Discovered in 1953 by Jacques Monod and colleagues.

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• The repressor for the trp operon is produced upstream by the

trpR gene, which is constitutively expressed at a low level.

• When tryptophan is present, these tryptophan repressor

dimers bind to tryptophan, causing a change in the repressor
conformation, allowing the repressor to bind to the operator
• This prevents RNA polymerase from binding to and
transcribing the operon, so tryptophan is not produced
from its precursor.

• When tryptophan is not present, the repressor is in its

inactive conformation and cannot bind the operator
region, so transcription is not inhibited
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REGULATION OF GENE EXPRESSION :

EUKARYOTES
In higher organisms signal molecule such as hormones or
second messengers function as inducers Eg. Steroiod

STAGES OF REGULATION OF GENE EXPRESSION IN

EUKARYOTES
• Chromatin remodeling
• Transcription
• Post transcriptional modification
• RNA transport
• Translation
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CHROMATIN REMODELING
• Transcription associated structural change in chromatin is
called chromatin remodeling.

• These include enzyme that covalently modify the core

histones of nucleosome

• The acetylation and deacetylation of histones figure

prominently in the processes that activate chromatin for
transcription.
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• Histone acetylation /deacetylation by histone acetyl

transferase and histone deacetylase enzyme

• Such modification decrease the positive charge of proteins,

thus decrease the strength of their association with negatively
charged DNA
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• Generally, increased acetylation is associated with increased

gene expression; coactivators often possess histone acetylation
(HAT)

• Decreased acetylation, or deacetylation is associated with

decreased gene expression; corepressors often possess histone
deacetylation.

• DNA methylation: A methyl group is added to the 5-carbon

position of cytosine residues in DNA.
DNA methylation is capable of inhibiting transcription
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TRANSCRIPTION
Transcription is the process of copying genetic
information stored in DNA into a transportable
complementary strand of RNA .
• Initiation
• Elongation
• Termination
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INITATION:
• First, an RNA polymerase along with general transcription
factors binds to the promoter region of the gene to form a
closed complex called the pre-initiation complex.

• RNA polymerase bind with the promoter site of DNA with the
help of transcription factors (TF II)

ELONG ATION:
• The RNA polymerase moves along a DNA template new
nucleotides are incoperated in nacent mRNA

• RNA polymerase moves on unwinding of DNA helix

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TERMINATION

• The last stage of transcription is termination, which leads to

the dissociation of the complete transcript and the release of
RNA polymerase from the template DNA.
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REGULATION OF TRANSCRIPTION
• RNA polymerase enzyme responsible for the synthesis of
eukaryotic mRNA
• Eukaryotic RNA polymerase have low or no affinity for their
promoters.
• Additional regulatory sequence required for transcripion is
enhancers
• A typical enhancer may be found 100 or even 1000 of base
pair upstream.
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PROMOTER
• Promoter is a region of DNA that initiates transcription of a
particular gene.
• Promoters are located near the transcription start sites of
genes.
• Promoters can be about 100–1000 base pairs long.
• In transcription , the enzyme that synthesizes RNA, known
as RNA polymerase, must attach to the DNA.
• Promoters contain specific DNA sequences such as response
elements that provide a secure initial binding site for RNA
polymerase.
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ENHANCER
• An enhancer is a DNA sequence that promotes transcription.
• Each enhancer is made up of short DNA sequences called
distal control elements.
• Enhancer regions are binding sequences, or sites, for
transcription factors.
• When a DNA-binding protein binds to an enhancer, the shape
of the DNA changes.
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For the successful binding of polymerase enzyme at one

of its promoter usually requires the action of other proteins.

• Basal transcription factors

• DNA binding trans-activators

• Co-activators
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• Basal transcription factors are proteins that bind to specific

DNA sequences within the promoter to facilitate RNA
polymerase alignment.

• Special trans-activators are proteins that bind to response

elements or to sequences called enhancers that are located
near a gene and facilitate the action of basal transcription
factors and RNA polymerase.

• Co-activators.
The latter group act indirectly—not by binding to the
DNA—and are required for essential communication
between the DNA-binding trans activators and the complex
composed of Polymerase II and the general transcription
factors.
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POST TRANSCRIPTIONAL
MODIFICATION
• Transcription of eukaryotic genes leaves a primary transcript
of RNA (pre-mRNA), which first has to undergo a series of
modifications to become a mature mRNA

These include
• 5' capping
• 3' cleavage and polyadenylation
• RNA splicing
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5ʹcapping
• Which is set of enzymatic reactions that add 7-
methylguanosine) to the 5' end of pre-mRNA .

• protect the RNA from degradation by exonucleases.

• The m7G cap is then bound by cap binding

complex heterodimer (CBC20/CBC80), which aids in mRNA
export to cytoplasm and also protect the RNA from decapping.
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3' cleavage and poly-adenylation

• They occur if poly-adenylation signal sequence (5'-

AAUAAA-3') is present in pre-mRNA, which is usually
between protein-coding sequence and terminator.

• The pre-mRNA is first cleaved and then a series of ~200

adenines (A) are added to form poly(A) tail, which protects
the RNA from degradation.

• Poly(A) tail is bound by multiple poly(A)-binding

proteins (PABP) necessary for mRNA export and translation
re-initiation
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RNA splicing
• The majority of eukaryotic pre-mRNA’s consist of alternating
segments called exons and introns.

• During the process of splicing two trans-esterification

reactions, which remove an intron and release it in form of
lariat structure, and then splice neighboring exons together.
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RNA TRANSPORT AND

LOCALISATION
• RNA localization is a widespread phenomenon that has
been observed in many eukaryotic cell types.

• RNA TRANSPORT : Fully processed RNA to must leave

the nucleus in order to be translated into proteins.

• Active targeting involves recognition of cis-acting RNA

elements.

• RNA segments that contain codes to specify targeting,

by trans-acting RNA-binding factors.
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• This interaction results in the formation of ribonucleotide

protein (RNP) complexes.

• RNP travel along cytoskeletal filaments with the help of motor

proteins.

• At their destination sites, delivered transcripts are anchored

and are now ready for translation.
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REFERENCES
• D.M Vasudevan, S Sreekumari, Text book of Biochemistry, 3rd
edition, Jaypee brothers Medical Publishers, Page No 363 –
371
• M N Chatterjea,Rana Shinde, Text Book of Medical
Biochemistry, 8th edition, Jaypee brothers Medical Publisher,
Page No 247 - 258
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