EPIGENETICS

DEFINITION

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.
 Mechanisms of epigenetics
Epigenetic changes alter the physical
structure of DNA. One mechanism of an epigenetic
change is DNA methylation the addition of a
methyl group, or a "chemical cap," to part of the
DNA molecule, which prevents certain genes from
being expressed.

Another mechanism is Histone modification.

Histones are proteins that DNA wraps around.
(Without histones, DNA would be too long to fit
inside cells.) If histones squeeze DNA tightly, the
DNA cannot be "read" by the cell. Modifications
that relax the histones can make the DNA
accessible to proteins that "read" genes.
 EPIGENETICS & CANCER

Epigenetics
can play a role in the development of som
e cancers
. 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.
 DNA Methylation

Cytosine DNA methylation is a covalent

modification of DNA, in which a methyl group
is transferred from S-adenosylmethionine to the
C-5 position of cytosine by a family of
cytosine (DNA-5)-methyltransferases.

DNA methylation occurs almost exclusively at

CpG nucleotides and has an important
contributing role in the regulation of gene
expression and the silencing of repeated
elements in the genome.
 DNA Methylation Influences Cancer
Processes

DNA
Repair

Carcinogen Hormonal
Metabolism Regulation
DNA
Methylation

Differentiation
Cell Cycle

Apoptosis
 HISTONE MODIFICATION

When histones are tagged, or

acetylated, chromatin is open and
genes are potentially active;

When histones are not chemically

tagged, deacetylated, the chromatin
condenses and genes silenced.
 Epigenetic Modification: Non-coding
RNAs
A new mechanism for gene regulation

RNA which is not used for making proteins (non-

coding RNA) can be cleaved and used to inhibit
protein-coding RNAs

microRNAs
 Methods to Study The Epigenome

Bisulphite sequencing
Methylation sensitive-High resolution
melting (MS-HRM)
Microarray-based genome-wide analysis
Chromatin immunoprecipitation (ChIP) on
Chip assays