EPIGENETICS

BY:- NOOR SABAH

 ?What is Epigenetics
 Epigenetics literally means "above" or "on top of"
genetics. It refers to external modifications to DNA
that turn genes "on" or "off." These modifications
do not change the DNA sequence, but instead, they
affect how cells "read" genes.
 The term epigenetics refers to heritable changes in
gene expression (active versus inactive genes) that
does not involve changes to the underlying DNA
sequence; a change in phenotype without a change
in genotype.
 Epigenetic change is a regular and natural occurrence
but can also be influenced by several factors including :-
• Age
• The environment/lifestyle and
• Disease state.
 Epigenetic modifications can manifest as commonly as
the manner in which cells terminally differentiate to
end up as skin cells, liver cells, brain cells, etc.
  Epigenetic change can have more damaging effects that
can result in diseases like cancer.
 At least three systems including
• DNA methylation
• histone modification and
• non-coding RNA (ncRNA)
 ?How does epigenetics works
 An epigenome consists of a record of the chemical changes to
the DNA and histone proteins of an organism
 When epigenomic compounds attach to DNA and modify its
function, they are said to have "marked" the genome. These
marks do not change the sequence of the DNA. Rather, they
change the way cells use the DNA's instructions. The marks
are sometimes passed on from cell to cell as cells divide. They
also can be passed down from one generation to the next.
 Epigenetic tags act as a kind of cellular memory. A cell's
epigenetic profile -- a collection of tags that tell genes
whether to be on or off -- is the sum of the signals it has
received during its lifetime.
  The Changing Epigenome Informs Gene Expression
MECHANISMS OF EPIGENETICS

1- DNA METHYLATION

2- HISTONE MODIFICATION

3- NON-CODING RNA (NCRNA)-

ASSOCIATED GENE
 DNA methylation
 DNA methylation is an epigenetic mechanism used by cells to control gene
expression. A number of mechanisms exist to control gene expression in
eukaryotes, but DNA methylation is a commonly used epigenetic signaling
tool that can fix genes in the “off” position.
 DNA methylation is a biological process by which methyl groups  are added
to the DNA molecule. Methylation can change the activity of a DNA segment
without changing the sequence. When located in a gene promoter DNA
methylation typically acts to repress gene transcription.
 In mammals, DNA methylation is essential for normal development and is
associated with a number of key processes including:-
•  genomic imprinting
•  X-chromosome inactivation,
• repression of transposable elements
•  aging, and carcinogenesis
 Two of DNA's four bases, cytosine and adenine, can be methylated. Cytosine
methylation is widespread in both eukaryotes and prokaryotes
 DNMT
 In mammalian cells, DNA methylation occurs mainly at the C5 position
of CpG dinucleotides and is carried out by two general classes of
enzymatic activities – maintenance methylation and de
novo methylation.
 Maintenance methylation activity is necessary to preserve DNA
methylation after every cellular DNA replication cycle. Without the 
DNA methyltransferase (DNMT), the replication machinery itself would
produce daughter strands that are unmethylated and, over time, would
lead to passive demethylation.
 DNMT1 is the proposed maintenance methyltransferase that is
responsible for copying DNA methylation patterns to the daughter
strands during DNA replication.
 It is thought that DNMT3a and DNMT3b are the de
novo methyltransferases that set up DNA methylation patterns early in
development.
 Histone Modification
 Histones are subject to a wide variety of
posttranslational modifications including but not limited
to:-
• lysine acetylation,
• lysine and arginine methylation,
• serine and threonine phosphorylation, and
• lysine ubiquitination and
• sumoylation .
 These modifications occur primarily within the histone
amino-terminal tails protruding from the surface of the
nucleosome as well as on the globular core region.
 Histone modifications are proposed to affect
chromosome function through at least two
distinct mechanisms:-
 The first mechanism suggests modifications
may alter the electrostatic charge of the histone
resulting in a structural change in histones or
their binding to DNA.
 The second mechanism proposes that these
modifications are binding sites for protein
recognition modules, such as the bromodomains
or chromodomains, that recognize acetylated
lysines or methylated lysine, respectively.
 Non-coding RNA (ncRNA)-associated gene 
 miRNAs or ncRNA represent small RNA molecules encoded
in the genomes of plants and animals. These highly
conserved 22 nucleotides long RNA sequences regulate the
expression of genes by binding to the 3'- untranslated
regions (3'-UTR) of specific mRNAs. A growing body of
evidence shows that miRNAs are one of the key players in
cell differentiation and growth, mobility and apoptosis
(programmed cell death).
 miRNAs regulate diverse aspects of development and
physiology, thus understanding its biological role is proving
more and more important. Analysis of miRNA expression
may provide valuable information, as dysregulation of its
function can lead to human diseases such as cancer,
cardiovascular and metabolic diseases, liver conditions and
immune dysfunction
 Epigenetics and Cancer

 Scientists now think epigentics can play some role

is the development of some cancer. For instance, an
epigenetic change that silences a tumor suppressor
gene — such as a gene that keeps the growth of the
cell in check — could lead to uncontrolled cellular
growth. Another example might be an epigenetic
change that "turns off" genes that help repair
damaged DNA, leading to an increase in DNA
damage, which in turn, increases cancer risk.
 Mental Retardation Disorders

  In these imprint disorders, there is a genetic

deletion in chromosome 15 in a majority of
patients. The same gene on the corresponding
chromosome cannot compensate for the
deletion because it has been turned off by
methylation, an epigenetic modification.
 Genetic deletions inherited from the father
result in Prader-Willi syndrome, and those
inherited from the mother, Angelman syndrome
 Neuropsychiatric Disorders
 Epigenetic errors also play a role in the causation of:-
• complex adult psychiatric,
• autistic, and
• neurodegenerative disorders.
• Several reports have associated schizophrenia and mood
disorders with DNA rearrangements that include the
DNMT genes.
 DNMT1 is selectively overexpressed in gamma-
aminobutyric acid (GABA) interneurons of schizophrenic
brains, whereas hypermethylation has been shown to
repress expression of Reelin (a protein required for normal
neurotransmission, memory formation and synaptic
plasticity) in brain tissue from patients with schizophrenia
and patients with bipolar illness and psychosis
 Application of Epigenetics

 Chemicals that enter our bodies can also affect the epigenome. Bisphenol A
(BPA) is a compound used to make polycarbonate plastic. It is in many
consumer products, including water bottles and tin cans.
 In the laboratory, BPA appears to reduced methylation of the agouti gene.
In the strain of mice that was studied, yellow mothers give birth to pups
with a range of coat colors from yellow to brown. When mothers were fed
BPA, their babies were more likely to be yellow and obese.
 However, when mothers were fed BPA along with methyl-rich foods, the
offspring were more likely to be brown and healthy.
 The maternal nutrient supplementation had counteracted the negative
effects of exposure
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