This document discusses various mechanisms of gene expression regulation in prokaryotes. It introduces the concepts of induction and repression using the example of beta-galactosidase in E. coli. Inducers activate gene expression while corepressors repress it. The operon model of the lac and tryptophan operons is explained in detail. Other mechanisms discussed include transcriptional, translational, and post-transcriptional regulation. Feedback inhibition is also summarized.

2. Contents
 Introduction
 Induction and Repression
 Inducer and Co-Repressor
 Types of regulation of Gene expression
 Transcriptional regulation: The Operon model
 Translational control
 Post Transcription regulation

3. Introduction
What is Gene Expression?
 Gene expression is the process by which the
information encoded in gene is used to direct
the assembly of a protein molecule.
What is regulation of gene expression?
 Regulation of gene expression includes a
wide range of mechanism that are used by
cells to increase or decrease the production
of specific gene products (protein or RNA).

4. Induction and Repression
 In E.Coli, synthesis of β-galactosidase an
enzyme meant for hydrolysis of lactose into
glucose and galactose, was studied in
considerable detail as early as 1960’s.
lactose β-galactosidase glucose +
galactose
 Such enzyme whose synthesis can be
induced by adding the substrate are known
as inducible enzyme and the genetic
systems responsible for the synthesis of
such enzyme are known as inducible

5. Cont…
 Such enzyme whose synthesis can be
restricted by adding end product of the
corresponding biosynthetic pathway, are
known as repressible enzyme and these
genetic system would be known as
repressible system.

6. Inducer and Co-Repressor
 The substrate whose addition induces
synthesis of an enzyme is called Inducer.
 The end product, whose addition will restrict
the synthesis of biosynthetic enzyme is known
as Co-Repressor.
 Although ordinarily only a substrate acts as an
inducer, but rarely there are molecules that
adequately resemble the natural inducer, but
are not metabolized themselves by the enzyme.

7. Cont…
A] In an inducible system :
active repressor +inducer ===> inactive
repressor
B] In an repressible system :
inactive repressor + Co-Repressor ===>
active repressor

8. Types of regulation of Gene
expression
A} Positive regulation
:-
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.

9. Cont…
B} Negative regulation:-
When the expression of
genetic information
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
repressior

10. Transcriptional regulation
The Operon Model
 F. Jacob and J. monod in1961, on the basis of
their study on the inducible system for the
synthesis of β-galactosidase enzyme in E.Coli
proposed a model to explain the induction or
repression of enzyme synthesis this model
popularly known as “Operon model” assumed
the presence of a unit called ‘operon’.

11. Cont…
 Operon consisting of two type of gene
1] An operator gene : which controlled the
activity of protein
2] structural gene : which take part in the
synthesis of protein

12. The PaJaMo Experiment:
(Discovery of mRNA and repressor)
 The key experiment is understanding of the
regulation of the expression of galactosidase
gene was actually conducted by three
scientists , namely Pardee, Jacob and Monod.
 In this experiment they used two strain:
A] Strain A :- is a donor strain that was Lac+ and
streptomycin susceptible
B] Strain B :- is a recipient strain that was Lac‾
and streptomycin resistance.

14. Cont…
Result of PaJaMo experiment :-
1] The Z gene was expressed very fast and at
maximum rate from the beginning, leading to
the formulation of mRNA hypothesis.
2] The inducible allele of the І gene ( І‾) was
dominant with respect to the constitutive allele
(І‾), but this dominance was expressed very
slowly, suggesting that this gene І was
responsible for the synthesis of a product that
inhibited/ repressed the biosynthesis of β-
galactosidase

15. Lac Operon
An operon as earlier mentaioned consists of
an operator and structural genes.
The Lac operon contain 26 base pairs.
In this operon there are three structural genes
including the following.
І] Lac Z gene :- code for β-galactosidase.
ІІ] Lac Y gene :- code for β-galactose permease
ІІІ] Lac A gene:- code for β-galactose transacetylase

16. Cont…
Any mutation of Lac Z and Lac Y genes give
Lac‾ genotypes, which can not utilize lactose.
In the Lac operon in E.coli repressor is
synthesized through activity of a gene Lac І .
A promoter gene located upstrem controls the
activity of the regulator gene.
The normal inducer of the Lac operon is
allolactose, which is produced from lactose by
β-galactosidase.
When allolactose combine with the repressor a
steric change occurs that cause the repressor
to be released frome the operator.

17. Cont…
 It has been found that a mutation in regulator
gene Lac І results in the absence of active
repressor and consequently lead to
uncontrolled synthesize enzyme independent
of need are known as constitutive strains or
constitutive mutants.
 Therefore, there are two types of constitutive
strains :
i} Regulator constitutive
ii} Operator constitutive
 Promoter gene : While operator gene is the
site of action of repressor, the actual site of
transcription start is different and is known as
promoter which is lies upstream of the
operator gene.

18. Cont..
 Associated with the Lac operon there is
another site 16 base pairs upstream of the
promoter which is used for a positive control
of a gene expression. This called catabolite
activator protein or cyclic AMP protein (CAP).
 There are two proteins for the regulation of
lactose operon:
i) Lac repressor
ii) catabolite gene activator protein (CAP)
 Uninducible mutant : uninducible mutant in the
Lac operon are those which can not can be
induced into synthesis of enzyme even on
addition of lactose.

20. Tryptophan operon
 The five structural genes that are involved in
the synthesis of tryptophan form an operator
and code for three enzyme needed for
tryptophan synthesis.
 A repressor is coded by a gene trp R, which is
not linked with the operon.
 The level of tryptophan besides working as a
co-repressor, also function through feedback
inhibition where tryptophan combines with the
first enzyme of tryptophan synthetic pathway
and inhibits its activity through allosteric
modifications.

22. Translational control
 In prokaryotic gene regulation at the
translational level, the life time of a mRNA
molecule may be genetically determined.
 Enzymatic degradation of mRNA from the 5’ to
the 3’ end.
 The specific nucleotide sequences at the 5’
end may influence its susceptibility to
enzymatic digestion.
 Hence the lifetime of mRNA may also be
correlated with the number of free ribosomes
available at any given moment to translate
mRNA molecule

23. Post Transcriptional regulation
 Autogenous regulation of translational:
 Several proteins work as repressors, bind to
the ribosome binding site or initiation codon of
mRNA.
 In these cases mRNA remains intact but can
not be translated.
 There are some other systems where mRNA
may be degraded by the binding on protein on
the short specific sequences of mRNA

24. Cont…
Regulation by Anti-sense RNA:
 Transcriptional control of protein synthesis
can be exercised by using RNA which is
complementary to mRNA, these
complementary RNA will form RNA-mRNA
hybrids and prevent mRNA from being
translated.
 These kind of RNAs are called anti-sense
RNA or micRNA. ( mic =mRNA interfering
complemetaryRNA)

25. Cont….
Repression of Translation :
 Repression of translation occurs by the
following ways :
a) A repressor effecter molecule may
recognize and bind to a specific sequence
or to a specific secondary structure, thus
blocking initiation of translation through
blocking of the ribosomal binding region.
b) A repressor effecter molecule may bind to
an operator thus stabilizing an inhibitory
mRNA secondary structure.
c) An effecter molecule can inhibit initiation of
translation by endonucleolytic cleave of SD
region.

26. Cont…
Activation of translation :
 Some positive effectors or activators cause
activation of translation by destabilizing the
inhibitory secondary structures in mRNA
either through simple binding or by
endonucleolytic cleavage.
 Translation of certain genes may be
influenced by certain other genes – the
phenomenon is called translational coupling.

27. Cont…
Feedback Inhibition :
 In some case, the end product of a particular
biosynthetic pathway gets accumulated and
this accumulation may stop further
synthesis of this substance.
 The end product acts through allosteric
transformation of the first enzyme of
biosynthetic pathway.

29. References :
 Genetics
By P K Gupta
 Cell biology, Molecular Biology,
Evolution and Ecology
By P. S. Verma &V. K. Agarwal
 www. slideshare.in
 www. regulation of gene expression
in prokaryotes images.in