In the field og genetics study, epigenetics can be defined as the study of the heritable variations in the expression of gene or cellular phenotype caused by the mechanisms other than the changes in underlying DNA sequence - so the name epi- (which means in Greek: above, or over, or outer) -Genetics . Ex: of such epigenetic changes are DNA methylation , histone deacetylation. In 2011, it was very recently elucidated that mRNA methylation has a crucial role in the human energy homeostasis. This lead to the evolution of RNA epigenetics.(1)
*Epigenetics:It is the branch that doesn't involve the variations in the sequence of DNA, it is known to be involved in the disease.2 main important epigenetic changes that are known to contribute to the disease are abnormal methylation patterns of the DNA and the modifications of the histones in the chromatin material. (1)
*A new upliftment in the field of the pharmacology, called as epigenetic therapy, will attempt to correct these particular changes . At present 2 drug classes are being developed . In that one inhibits the enzyme DNA methyl transferases which will result in the inhibition of methylation of DNA . (1)
*This novel batch of drugs may prove to be useful in the process of treating cancer where as hyper methylation of tumour suppressor will lead to silencing of these genes. The second batch of drugs will inhibit the enzymes namely histone deacetylases (HDACs) which will result in the accumulation of the acetylated histones which will interconnect the anticancer effects of these batch drugs.these both drug groups shows many promising results in the drug trials for treatment of the cancer. The scope of Epigenetics is likely to expand. (1)
*The disease here involved was cancer, and to note the majority of the diseases in which the epigenetic defects are shown to be involved in diseased pathogenesis are mostly cancers. Epigenetics plays a main role in the pathogenesis of general, many factorial disorders. For instance, there is proof in suggesting that the primary (i.e.,idiopathic disorders namely Schizophrenia and also another disorder namely bipolar disorder are due to the reason of the epigenetic defects than that of the genetic factors. (1)
Epigenetics and its molecular aspects:
* The general concepts and the molecular aspects of epigenetics are rapidly evolving in these days. 3 main molecular mechanisms namely ,DNA methylation, histone modification , and RNA-associated silencing, which interact with each other, are involved. (2)
* The process namely DNA methylation which generally but not always depends on position of the methylation change in relation to the position of initiation of the transcription site, will inhibit the gene transcription process.
*Histone proteins can be modified by several methods like methylation, acetylation, and phosphorylation. The Acetylation process of the histone proteins which happens at lysine residues and it will be regulated by a histone acetyl transferases and it is linked with the activation of the gene transcription process. (2)*
A 3rd mechanism of the epigenetics in this gene expression process is the silencing of the genes with the RNA-association has recently came up.
The pharmacological application of epigenetics-EPIGENETIC THERAPY :
*Epigenetic therapy, the application of the specific drugs to correct the epigenetic defects, it is a novel and rapidly evolving area of the branch pharmacology. Epigenetic therapy is potentially very useful form of the therapy because of the epigenetic defects, when compared to the genetic defects, are more easily reversible with pharmacological intervention. Besides holding promise as the therapeutic agents, epigenetic drugs are able to prevent disease. However, epigenetic therapy has its own disadvantages, such as both DNMT as well as the HDAC inhibitors may activate the cancer causing oncogenes due to the absence of specificity, that results in the accelerated and also , epigenetic states, once corrected, may revert to its original state because of the reversible nature of methylation patterns of DNA. (3)
*Many potentially useful epigenetic drugs are presently undergoing preclinical and clinical drug trials. Most of these trials have involved many types of cancers like solid tumours and haematological malignancies (tumours). (3)
Epigenetic therapy-It is a new and developing area in the field of pharmacology. Till date, most trials of the epigenetic drugs are conducted to evaluate their effects on the cancers, many of which showed promising results. Adverse effects are more in case of traditional drugs (4)*
Only Epigenetiic drugs or these epigenetic drugs in association with the conventional or traditional are the anticancer drugs may prove to be an important advance when compared to the conventional or traditional anticancer drugs . As the epigenetic defects are though to underlie a broad range of the diseases , the scope of this epigenetic therapy is more likely to expand. (4)
1.http://en.wikipedia.org/wiki/Epigenetics (accessed on 20/11/11:8:47p.m)
2.http://icmr.nic.in/ijmr/2006/january/0106.pdf(accessed on 20/11/11:8:47p.m)
3.http://www.mendeley.com/research/epigenetic-therapya-new-development-in-pharmacology/( accessed on 20/11/11:8:47p.m)
4.http://www.citeulike.org/user/Rohdium/article/6583504(accessed on 20/11/11:8:47p.m)
5.http://scienceblogs.com/pharyngula/2008/07/22/epigenetics.jpg(accessed on 20/11/11:8:47p.m)
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