PBL!
PBL!
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’’.
Environmental Drugs
Development chemicals
Aging Diet
DNA Modifications
methylation in Histones
Epigenetics
Mod. Of
DNA
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.
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:
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
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.
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