CSE-303 Hall, Department of CSE, NIT Calicut.
April 16, 2014
Regulation of Gene Expression
Tanuj Kumar Jhamb
MTECH Ist Year
M130190 CS
DEPARTMENT OF Computer Science and Engineering
NIT CALICUT
tkjakaa@gmail.com
Abstract— It has been suggested that evolutionary
changes in gene expression account for all living organism
either eukaryotes or prokaryotes. Process of alteration of
gene expressision has been studied in detail & involves
modulation of gene transcription control that can result in
tissue specific to gene expression and influenced by
hormones,heavy metals. In simple terms,regulation of
gene expression is of two types 1.positive regulation,
2.negative regulation. When the expression of genetic 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 diminished by the presence of specific
regulatory element. The element or molecule mediating
the negative regulation is said to be repressor. Many
genetic variants associated with common disease
susceptibility occur close to immune-related genes in
noncoding DNA, suggestive of a regulatory function. The
definition of functional variants and the specific genes that
they regulate remains challenging and in many cases is
unresolved. We hypothesized that a significant proportion
of variants, including those implicated in disease, may
show activity in a context-specific manner and therefore
only be identifiable upon triggering of immune responses.
Index Terms—Gene Regulation, operon, E.coli, Tryptophan
operon, DNA Methylation, mRNA acetylation, Gene
Aplification, Histone.
I. INTRODUCTION
Gene Expressionis 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 rRNA genes or tRNA genes, the products are
functional RNA. Genome is the genetical material present in
all living organism. Different cells contain the same genome,
but they express different RNAs and proteins. The Gene
Expression can be different for the cells genome. If the
functional gene product is different then the Gene Expression
will also be different. Transcription in prokaryotes is carried
out by a single type of RNA polymerase, which needs a DNA
sequence called a Pribnow box as well as a sigma factor to
start transcription. In eukaryotes, transcription is performed
by three types of RNA polymerases, each of which needs a
special DNA sequence called the promoter and a set of DNA-
binding proteins and transcription factors to initiate the proc-
ess. RNA polymerase I is responsible for transcription of
ribosomal RNA (rRNA) genes. RNA polymerase II (Pol II)
transcribes all protein-coding genes. Transcription ends when
the polymerase encounters a sequence called the terminator. A
very important modification of eukaryotic pre-mRNA is RNA
splicing. The majority of eukaryotic pre-mRNAs consist of
alternating segments called exons and introns. During the
process of splicing, an RNA-protein catalytical complex
known as spliceosome catalyzes two transesterification
reactions, which remove an intron and release it in form of
lariat structure, and then splice neighbouring exons together.
In certain cases, some introns or exons can be either removed
or retained in mature mRNA. This so-called alternative
splicing creates series of different transcripts originating from
a single gene. Because these transcripts can be potentially
translated into different proteins, splicing extends the
complexity of eukaryotic gene expression. Extensive RNA
processing may be an evolutionary advantage made possible
by the nucleus of eukaryotes. In prokaryotes transcription and
translation happen together whilst in eukaryotes the nuclear
membrane separates the two processes giving time for RNA
processing to occur.
II. GENE REGULATION
 Gene Regulation includes a various methods that are used
by cells/viruses to increase or decrease the production of
specific gene products (protein or RNA). Although a
functional gene product may be an RNA or a protein, the
majority of known methods 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. 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. The first discovered(1953) example of a
gene regulation system was the lac operon in prokaryotes,
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. For some RNA
(non-coding RNA) the mature RNA is the final gene product.
[8] In the case of messenger RNA (mRNA) the RNA is an
information carrier coding for the synthesis of one or more
proteins. mRNA carrying a single protein sequence (common
in eukaryotes) is monocistronic whilst mRNA carrying
multiple protein sequences (common in prokaryotes) is
known as polycistronic. Several steps in the gene expression
process may be modulated for Gene Regulation, including the
transcription, RNA splicing, translation and post-translational
modification of a protein.
Furthermore, 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. Biological systems exhibits 3 types of temporal
responses: Type A response increses the extent of gene expre-
ssion is continued in presence of inducing signal. This is
commonly observed in prokaryotes in responce to intra-
cellular conc. Of nutrient. TYPE B response increases the
amount of gene expression is the transient even in presence of
regulatory signal. This is seen in commonly during
development of organism. Type c response increases the gene
expression that persists even after termination of signal. It is
seen in development of tissue or organ.
III. PRINCIPLE OF GENE REGULATION
Genes are composed of DNA, which contains information
coded in the base pair sequences. They are then used as the
blueprint for protein synthesis (gene expression). DNA
consists of nucleic acid, adenine(A), guanine(G), cytosine(C),
and thymine(T); while RNA consists of nucleic acid,
adenine(A), guanine(G), cytosine(C), and uracil (U). RNA is
usually single stranded while DNA is always double stranded.
RNA can be found in both the nucleus and the cytoplasm.
There are several types of RNA, all of which are involved in
some aspect of protein synthesis: mRNA, tRNA, and rRNA.
1) RNA polymerase binds to DNA at promoters.
2) Transcription initiation is regulated by proteins that bind
to or near promoters.
3) Repression of a repressible gene:(i.e. negative
regulation).
4) Repressors (vs. activators) bind to operators of DNA.
5) Repressor is regulated by an effector, usually a small
molecule or a protein, that binds and causes a functional and
structural change.
6) Activator binds to DNA sites called enhancer, such that
they enhance the RNA polymerase activity (i.e. positive
regulation). Induction of an inducible gene, e.g., heat-shock
genes.z
The regulation of gene expression (transcription) enables
prokaryotes to control their metabolism. Regulation of
transcription is based on the accessibility of RNA polymerase
to the gene being transcribed and is directed by an operon,
which consists of structural genes, an operator gene, and a
promoter gene. Structural genes contain sequences of DNA
that encode for proteins. The operator gene is the sequence of
nontranscribable DNA that is the repressor binding site. The
promoter gene is the noncoding sequence of DNA that serves
as the initial binding sit for RNA polymerase. There is also a
regulator gene, which codes for the synthesis of a repressor
molecule hat binds to the operator and blocks RNA
polymerase from transcribing the structural genes.
IV. GENE REGULATION IN EUKARYOTES
Mostprokaryotic genes are regulated in units called op-
erons[1]. Operons are simply a sequence of gene which acts
as promotor. Prokaryotes lead erate to Polycistronic mRNA's.
Eukaryotes lead generate to Monocistronic mRNA's. A few
genes that are controlled collectively by one promoter Its
structure: Each Operon is consisted of few structural
genes(cistrons) and some cis-acting element such as promoter
(P) and operator (O). There are one or more regulatory gene
outside of the Operon that produce trans-acting factors such
as repressor or activators. It can be classified into Catabolic
(inducible) such as Lac OPERON[2] and Anabolic (repr-
essible) such as ara OPERON. There are one or more
regulatory gene outside of the Operon that produce trans-acti-
ng factors such as repressor or activators. Lac operon (lactose
operon) is an operon required for the transport and
metabolism of lactose in E.coli[3] and some other bacteria. It
has three adjacent structural genes, lacZ, lacY, and lacA. Its
structure consist of each lac Operon is consisted of few
structural genes( cistrons) and some cis-acting element such
as promoter(P) and operator(O). The mRNA degradation
control is electively destabilizing certain mRNA molecules in
the cytoplasm the stability of different mRNAs in the
cytoplasm varies widely. There are many eukaryotic mRNAs
are quite stable, some have unusually short half-lives. The
stability is determined by the cap-structure and the length of
the poly-A tail of the mRNA. The mRNA degradation is
carried out by ribonucleases (deadenylation, degradation of
the poly-A tail). The mRNA stability is also dependent on
base pair structure of the Translational control selecting which
mRNAs in the cytoplasm are translated by ribosomes
Mechanisms of translation control.
Eukaryotic Terminology
1. Transcription Control:
The transport control (only the mRNA which is transported
to the ytoplasm can be transl-ated) number of ribosomes
translation factors (if the concentration of these factors is too
low in the cell, the translation start or the elongation process
can be decelerated or inhibited, mRNA localisation (a specific
place in the cytoplasm leads to the production of the protein at
a specific position in the cell)formed Regulation by
untranslated regions (UTRs).
2. DNA methylation:
It is the addition of a methyl group (CH3) to the DNA's
cytosine base. Most likely on consecutive Cytocine base pair.
Heterochromatin is the most tightly packaged form of DNA
transcriptionally silent, different from cell to cell. Methylation
is related to the Heterochromatin formation. Small
percentages of newly synthesized DNAs (~3% in mammals)
are chemically modified by methylation. Methylation occurs
most often in symmetrical CG sequences. Transcriptionally
active genes possess significantly lower levels of methylated
DNA than inactive genes. Methylation results in a human
disease called fragile X syndrome; FMR-1 gene is silenced by
methylation.
3. Histone Acetylation:
Nucleosomes are portions of double-stranded DNA
(dsDNA) that are wrapped around protein complexes called
histone. Acetylation is adding of acetyl group to the bases,
which result into Regualtion of Gene. It can be done during
RNA polymerization. Histone acetylation is catalyzed by
histone acetyltransferases (HATs) and histone deacetylation is
catalyzed by histone deacetylases (denoted by HDs or
HDACs). Histones are small proteins that mediate the folding
of DNA into chromatin, DNA is wrapped around octamers of
core histones.
V. GENE AMPLIFICATION
Gene Amplification[4]. A selective increase in the number
of copies of a gene coding for a specific protein without a
proportional increase in other genes that can be done by
Proteolysis reaction. Gene amplification, also known as gene
duplication or chromosomal duplication, is a cellular process
in which multiple copies of a gene are produced. Repeated
rounds of DNA replication yield multiple copies of a
particular chromosomal region. It is very efficient and
accurate way.
It repeats round of DNA replication yield multiple copies of a
particular chromosomal region.Ubiquitin-depe-ndent prote-
olysis. Cyclins control of cell cycle. Protein mole-cule is tag- [4] R H Don, P T Cox, B J Wainwright, K Baker, J S Mattick “Touchdown
PCR to circumvent spurious priming during gene amplification”
ged for degradation by attachment of a 20 kDa prot-ein, ubiq- Nucleic Acids Res. 2013 July 25; 19(14): 4008. PMCID: PMC328507
uitin. [5] Flores M1, Hsiao TH, Chiu YC, Chuang EY, Huang Y, "Gene
regulation, modulation,and their applications in gene expression data
analysis" University of Texas at San Antonio, Advances in
Bioinformatics Volume 2013 (2013), Article ID 360678, 11 pages
VI. PROPOSED IDEA
[6] http://www.ncbi.nlm.nih.gov
Gene amplification is best approach so far, for regulation [7] Harper’s illustrated biochemistry
of Gene Expression. Here in paper[5], They are amplifying [8] Genes IX.
[9] Molecular Biology Of Cell 4th edition(Book)
gene through this Proteolysis reaction. I suggest if we use [10] Concepts of genetics(Book)
hardware amplifying chip, which can give better performance. [11] http://www.hschickor.de/animat.htm
It costs expensive but helps a lot for regulating a gene. By [12] http://en.wikipedia.org/wiki/Amplifier
making some chip like microarray, and give DNA sequence as
input, we can implement some Gene Regulating chip. By
simulating this proteolysis reaction into a chip will result into
an quite efficient way of regulating gene. Some Advantages
are once the circuit is designed, it is easy to manage. It can be
used to amplify long length dna sequence at low frequency
signal. Some disadvantages are that is is very Expensive, this
can be used at high temperature also So it'll cause aging of
components due to temperature variations etc.

VII. APPLICATIONS
It can be used for the Analysis of Gene Expression in
Cancer. Gene can be regulated for reducing the genetic hair
fall. Hereditary disease can be avoided by regulatig the gene
of offsprings.Enhancers contain short sequence elements,
some similar to promoter sequences. Activators bind these
sequences and other protein complexes form, postulated to
bring the enhancer complex close to the promoter and increa-
sing transcription.

VIII. CONCLUSION
Gene regulation is the process of protein formation by
altering the transcription process. They carry out majority of
the processes that are important for life, as they include
enzymes, transcription factors and the various cell machinery.
Indeed, without proteins, life may not be a possibile. Operons
provide coordinated expression of genes which include
promoter, binding sites for activators and repressors, and
functional groupings of genes.

REFERENCES
[1] Socorro Gama-Castro1, Veronica Jimenez-Jacinto1, "RegulonDB
(version 6.0): gene regulation model of Escherichia coli K-12 beyond
transcription active (experimental) annotated promoters”,Universidad
Nacional Autónoma de México, A.P. 565-A, Nucl. Acids Res. (2012)
36 (suppl 1): D120-D124. Doi: 10.1093
[2] Michael Z, Ludwig, Manu, Ralf Kittler, Kevin P. White, Martin
Kreitman "Consequences of Eukaryotic Enhancer Architecture for
Gene Expression Dynamics, Development, and Fitness" Plos-Genetics,
November 2012 | Volume 7 | Issue 11 | e1002364
[3] RC Dickson, J Abelson, WM Barnes, WS Reznikoff "Genetic
regulation: the Lac control region" Science 10 January 1975: Vol. 187
no. 4171 pp. 27-35 DOI: 10.1126/science.108892