Epigene tics is defined as an event that is not principally governed by genetic principles, and is a study of stable and heritable changes in gene expression or phenotype without alteration to the Watson-Crick base-pairing of DNA.
These changes persist through a number of cell divisions and generations with no underlying changes in the DNA sequence. Therefore, epigenetics cannot be explained by genetic principles, and results in changes in gene expression are caused by casual interaction of genes and their by-products. A cells epigenetic landscape is governed by “chromatin” which is a complex of DNA and all its associated proteins including histones.
Much of today’s research in this field is focused on covalent and non-covalent modifications of primarily histones and DNA, which results in substantial changes in chromatin structure which in-turn may influence gene-activation/ repression. In addition to other post-translational modifications, the two most prominent ones include the histone acetylation, which correlates with gene expression and activation, and histone methylation which can either activate or silence genes based on a gene/ tissue specific histone methyl-mark, or the presence of a specific “histone-code” which would determine the overall fate of the cells gene expression profile. In general, histone acetylation leads to unwinding of the DNA around the histone thereby increasing access of transcription factors to the DNA, and facilitating gene expression. Histone methylation has variable effects; H3-K4 methylation corresponds to gene activation and H3-K9 methylation corresponds to gene silencing. These modifications are conserved and hence any dysregulation in this process can lead to altered gene function and malignant transformation of cells.
Cancer epigenetics reveals that the packaging and modifications of the “genome” is equally important to the “genome” by itself, in order to regulate normal cell functioning and key cellular processes. Recent studies indicate that cancer, initially thought of as a genetic disease is now also determined by gene alterations caused by reprogramming of the “epigenetic machinery”, which includes changes in DNA methylation, histone modifications, nucleosome positioning and non-coding RNAs, specifically microRNA expression. These epigenetic modifications are reversible as well, due to the presence of a number of histone deacetylases (HDACs), as well as histone and DNA demethylases. Hence the research field of “epigenetic therapy” aims at converting these epigenetic changes to the “normal epigenome” is very promising, as a number of drugs targeting “epigenetic therapy” are being approved by the FDA. There are several drugs currently undergoing clinical trials, including DNA methylase and HDAC inhibitors, which restore normal methylation and acetylation patterns. Recent studies also include histone methylase inhibitors and the use of miRNA’s to repress oncogenes.
BioVision offers a number of products for Epigenetics research including assay kits, recombinant proteins, antibodies, enzyme inhibitors and much more.
HATs
HDACs
Histones
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