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EPIGENETIC MODIFICATIONs

OF DNA

By PBL Group-5
Epigenetic modifications of DNA are the reversible, heritable changes in the DNA especially in the histone
proteins and the nucletides structure(methylation) without altering the nucleotide sequences in the DNA
for the purpose of regulation of gene expression.

Epigenetics refers to “ above genetics” as it donot alter gene sequence but only affects how the gene is
read by cells’’.

Factors affecting epigenetics modification of DNA include

Environmental Drugs
Development chemicals

Aging Diet
DNA Modifications
methylation in Histones

Epigenetics
Mod. Of
DNA

DNA methylation: It is the addition of methyl group to the 5’ carbon of cytosine


residues by a covalent bond.
In mammals cytosine methylation is restricted to CpGs sequences.The region of high
concentration of CpGs dinucleotides is called CpGs islands. About 70% of CpG sequence In
human are methylated and implicated in genomic imprinting which leads to choice of allelic
expression. Methylation of DNA is done by enzymes DNA methyl transferase.

Dna methylation cause silencing of genes . Promoters site in DNA are rich with CpG contents.
Methylated CpGs in DNA sequence prevent the binding of transcription factors at the
promoter sites and prevent transcription and hence the gene cannot be expressed at all.
Techniques to detect and measure the Dna Methylation in a Genome:
Modifications in Histones
dsDNA is wound around histones . There are 5 types of histone proteins .
H1,H2A,H2b,H3,H4.

The amino terminals of H2A and H2B are lysine rich where there is maximum
chance of acetylation and methylation.
Acetylation of Histones cause activation of translation.Acetylation at the
amino terminal of Histone proteins reduces the +charge of amine tails which
decreases the attraction to –ively charged DNA strand and hence helping in
unwounding of DNA during transcription.

On contrary , the deacetylation cause inactivation of transcription and


condensation of chromatin forming heterochromatins which are inactive
DNA contents.
Methylation of histones proteins also prevents the transcription and
hence non-expression of genes or repression of genes.
The good example of this is inactivation of one of X chromosomes in
females.

An additional way of Epigenetics repression of Genes


RNA associated silencing of Genes: Genes can be turned
off by RNA when it is in the form of antisense transcripts,
noncoding Rnas or Rna interference. RNA might affect
gene by causing heterochromatin formation,triggering
histone modification and DNA methylation.
Role of Epigenetics modification of DNA in positive sense:

Epigenetics modification cause silencing of Genes i.e a way of regulation of Gene Expression.
The silencing of certain genes are necessary at certain place and certain situation
Some important roles of Epigenetic Modifiaction Include:

Regulation of Tissue Specific Genes

One of two X chromosomes Inactivation


in female

Genomic Imprinting: It is the silencing of certain genes of


autosomal chromosome causing preferencial expression of one of
alleles in heterozygous condition of zygote. One of either paternal
or maternal allele is repressed in heterozygous fetus during
development according to law of dominance.
Adverse Effects Of Epigenetic Modification:

Cancer
It is the first human disease associated with Epigenetics. Methylation of tumor suppressr
genes can cause cancer to rise. In normal cell, the CpGs islands of promotor region of
tumor suppressor genes is unmethylated but in cancer cells are methylated . Also,
hypermethylation can increase instability of microsatellites(repeats of CA dinucleotides)
which are linked to cancers.

Mental Retardation:
Fragile X syndrome= it is characterized by intellectual disabilities, weak verbal
development and autistic like behaviour. Males are severly impacted since they have
only one chromosome. The X chromosome look very fragile under microscope –
appears as hanging by a thread and easily breakable.

Some other mental retardations include Prader –willi syndrome, Angelman Syndrome,etc.
Applied Epigenetics

Combating Diseases with Epigenetic Therapy:


We know many diseases such as cancers have epigenetic changes which are reversible unlike Dna
sequence mutations. We can use the knowledge of Epigenetics to reverse this changes.

Inhibitors of DNA methylation can induce expression of silenced genes. Examples of such inhibitors
are 5-azacytidine and 5-aza-2’-deoxycytidine.They act by inhibiting DNA methyl transferase enzymes.

Deacetylation oF Histones that cause silencing of Genes can be prevented by using HDAC inhibitors
which inhibits the HDAC(Histone Deactylase) enzymes from decetylating the histones.
THANK YOU

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