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 functional RNA. Genome is the genetical material present in
changes in gene expression account for all living organism all living organism. Different cells contain the same genome,
either eukaryotes or prokaryotes. Process of alteration of but they express different RNAs and proteins. The Gene
gene expressision has been studied in detail & involves Expression can be different for the cells genome. If the
modulation of gene transcription control that can result in functional gene product is different then the Gene Expression
tissue specific to gene expression and influenced by will also be different. Transcription in prokaryotes is carried
hormones,heavy metals. In simple terms,regulation of out by a single type of RNA polymerase, which needs a DNA
gene expression is of two types 1.positive regulation, sequence called a Pribnow box as well as a sigma factor to
2.negative regulation. When the expression of genetic is start transcription. In eukaryotes, transcription is performed
quantitatively increased by the presence of specific by three types of RNA polymerases, each of which needs a
regulatory element is known as positive regulation. special DNA sequence called the promoter and a set of DNA-
Element modulating positive regulation is known as binding proteins and transcription factors to initiate the proc-
activator or positive regulator. When the expression of ess. RNA polymerase I is responsible for transcription of
genetic information diminished by the presence of specific ribosomal RNA (rRNA) genes. RNA polymerase II (Pol II)
regulatory element. The element or molecule mediating transcribes all protein-coding genes. Transcription ends when
the negative regulation is said to be repressor. Many the polymerase encounters a sequence called the terminator. A
genetic variants associated with common disease very important modification of eukaryotic pre-mRNA is RNA
susceptibility occur close to immune-related genes in splicing. The majority of eukaryotic pre-mRNAs consist of
noncoding DNA, suggestive of a regulatory function. The alternating segments called exons and introns. During the
definition of functional variants and the specific genes that process of splicing, an RNA-protein catalytical complex
they regulate remains challenging and in many cases is known as spliceosome catalyzes two transesterification
unresolved. We hypothesized that a significant proportion reactions, which remove an intron and release it in form of
of variants, including those implicated in disease, may lariat structure, and then splice neighbouring exons together.
show activity in a context-specific manner and therefore In certain cases, some introns or exons can be either removed
only be identifiable upon triggering of immune responses. or retained in mature mRNA. This so-called alternative
splicing creates series of different transcripts originating from
Index Terms—Gene Regulation, operon, E.coli, Tryptophan a single gene. Because these transcripts can be potentially
operon, DNA Methylation, mRNA acetylation, Gene translated into different proteins, splicing extends the
Aplification, Histone. 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
I. INTRODUCTION membrane separates the two processes giving time for RNA
Gene Expressionis the process by which information from a processing to occur.
gene is used in the synthesis of a functional gene product.
These products are often proteins, but in non-protein coding II. GENE REGULATION
genes such as rRNA genes or tRNA genes, the products are
 Gene Regulation includes a various methods that are used responses: Type A response increses the extent of gene expre-
by cells/viruses to increase or decrease the production of ssion is continued in presence of inducing signal. This is
specific gene products (protein or RNA). Although a commonly observed in prokaryotes in responce to intra-
functional gene product may be an RNA or a protein, the cellular conc. Of nutrient. TYPE B response increases the
majority of known methods regulate protein coding genes. amount of gene expression is the transient even in presence of
Any step of the gene's expression may be modulated, from regulatory signal. This is seen in commonly during
DNA-RNA transcription to the post-translational modification development of organism. Type c response increases the gene
of a protein. Gene regulation is essential for viruses, expression that persists even after termination of signal. It is
prokaryotes and eukaryotes as it increases the versatility and seen in development of tissue or organ.
adaptability of an organism by allowing the cell to express
protein when needed. The first discovered(1953) example of a III. PRINCIPLE OF GENE REGULATION
gene regulation system was the lac operon in prokaryotes, Genes are composed of DNA, which contains information
discovered by Jacques Monod, in which protein involved in coded in the base pair sequences. They are then used as the
lactose metabolism are expressed by E.coli only in the blueprint for protein synthesis (gene expression). DNA
presence of lactose and absence of glucose. For some RNA consists of nucleic acid, adenine(A), guanine(G), cytosine(C),
(non-coding RNA) the mature RNA is the final gene product. and thymine(T); while RNA consists of nucleic acid,
[8] In the case of messenger RNA (mRNA) the RNA is an adenine(A), guanine(G), cytosine(C), and uracil (U). RNA is
information carrier coding for the synthesis of one or more usually single stranded while DNA is always double stranded.
proteins. mRNA carrying a single protein sequence (common RNA can be found in both the nucleus and the cytoplasm.
in eukaryotes) is monocistronic whilst mRNA carrying There are several types of RNA, all of which are involved in
multiple protein sequences (common in prokaryotes) is some aspect of protein synthesis: mRNA, tRNA, and rRNA.
known as polycistronic. Several steps in the gene expression
process may be modulated for Gene Regulation, including the 1) RNA polymerase binds to DNA at promoters.
transcription, RNA splicing, translation and post-translational 2) Transcription initiation is regulated by proteins that bind
modification of a protein. 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

Furthermore, gene regulation drives the processes of cellular

differentiation and morphogenesis, leading to the creation of
different cell types in multicellular organisms where the
The regulation of gene expression (transcription) enables
different types of cells may possess different gene expression
prokaryotes to control their metabolism. Regulation of
profile. Biological systems exhibits 3 types of temporal
transcription is based on the accessibility of RNA polymerase a specific position in the cell)formed Regulation by
to the gene being transcribed and is directed by an operon, untranslated regions (UTRs).
which consists of structural genes, an operator gene, and a
2. DNA methylation:
promoter gene. Structural genes contain sequences of DNA
that encode for proteins. The operator gene is the sequence of It is the addition of a methyl group (CH3) to the DNA's
nontranscribable DNA that is the repressor binding site. The cytosine base. Most likely on consecutive Cytocine base pair.
promoter gene is the noncoding sequence of DNA that serves Heterochromatin is the most tightly packaged form of DNA
as the initial binding sit for RNA polymerase. There is also a transcriptionally silent, different from cell to cell. Methylation
regulator gene, which codes for the synthesis of a repressor is related to the Heterochromatin formation. Small
molecule hat binds to the operator and blocks RNA percentages of newly synthesized DNAs (~3% in mammals)
polymerase from transcribing the structural genes. are chemically modified by methylation. Methylation occurs
most often in symmetrical CG sequences. Transcriptionally
active genes possess significantly lower levels of methylated
IV. GENE REGULATION IN EUKARYOTES DNA than inactive genes. Methylation results in a human
disease called fragile X syndrome; FMR-1 gene is silenced by
Mostprokaryotic genes are regulated in units called op-
methylation.
erons[1]. Operons are simply a sequence of gene which acts
as promotor. Prokaryotes lead erate to Polycistronic mRNA's. 3. Histone Acetylation:
Eukaryotes lead generate to Monocistronic mRNA's. A few Nucleosomes are portions of double-stranded DNA
genes that are controlled collectively by one promoter Its (dsDNA) that are wrapped around protein complexes called
structure: Each Operon is consisted of few structural histone. Acetylation is adding of acetyl group to the bases,
genes(cistrons) and some cis-acting element such as promoter which result into Regualtion of Gene. It can be done during
(P) and operator (O). There are one or more regulatory gene RNA polymerization. Histone acetylation is catalyzed by
outside of the Operon that produce trans-acting factors such histone acetyltransferases (HATs) and histone deacetylation is
as repressor or activators. It can be classified into Catabolic catalyzed by histone deacetylases (denoted by HDs or
(inducible) such as Lac OPERON[2] and Anabolic (repr- HDACs). Histones are small proteins that mediate the folding
essible) such as ara OPERON. There are one or more of DNA into chromatin, DNA is wrapped around octamers of
regulatory gene outside of the Operon that produce trans-acti- core histones.
ng factors such as repressor or activators. Lac operon (lactose
operon) is an operon required for the transport and V. GENE AMPLIFICATION
metabolism of lactose in E.coli[3] and some other bacteria. It Gene Amplification[4]. A selective increase in the number
has three adjacent structural genes, lacZ, lacY, and lacA. Its of copies of a gene coding for a specific protein without a
structure consist of each lac Operon is consisted of few proportional increase in other genes that can be done by
structural genes( cistrons) and some cis-acting element such Proteolysis reaction. Gene amplification, also known as gene
as promoter(P) and operator(O). The mRNA degradation duplication or chromosomal duplication, is a cellular process
control is electively destabilizing certain mRNA molecules in in which multiple copies of a gene are produced. Repeated
the cytoplasm the stability of different mRNAs in the rounds of DNA replication yield multiple copies of a
cytoplasm varies widely. There are many eukaryotic mRNAs particular chromosomal region. It is very efficient and
are quite stable, some have unusually short half-lives. The accurate way.
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 It repeats round of DNA replication yield multiple copies of a
place in the cytoplasm leads to the production of the protein at 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