Dynamism Of Epigenetics
You may have heard the fascinating term epigenetics in news articles or scientific journals as a miracle panacea for every disease. But wait a second, let me decipher this tough term for you. The literal mean of ‘Epi’ is above and ‘genetics’ is the study of heredity and the variation of inherited characteristics. Thus, epigenetics can be described as the additional information layered on top of the genetic material (DNA) that determines how the information in the genes (made up of DNA) is read by the cells. These epigenetic changes hold the capacity to decide which proteins to be transcribed or not. Take an instance, many of you replicate the recipes that you watch on cooking channel. Some of you would add the same amount of ingredients as suggested but few might just add little less salt or some extra spices. Similarly, your phenotype is the result of switching on and off your 20,000 genes with regards to your milieu, food you eat and the lifestyle choices you make.
Epigenetic changes allow different cells from same individual to behave profoundly different from each other, despite carrying essentially the same DNA sequence. For example, your liver and skin cells are genetically identical, however they don’t necessarily follow the same steps of the instruction manual and become specialized in their own way, process known as cell differentiation. The basis of epigenetics is the covalent chemical modifications of DNA itself or the histones hugging the DNA string. Addition of these chemicals tags like methyl, acetyl, ubiquitin or a phosphoryl group can choose to activate or repress the function of certain genes and these outcomes can be transmitted to daughter cells, although many researchers report that some epigenetic changes are reversible.
Hopefully, by now I have piqued your interest in this field. Let’s take a look at how changes in epigenetics may lead to undesired outcomes. Epimutations cause complex disorders like Prader-Willi syndrome and Angelman syndrome due to errors in genomic imprinting with loss of imprinted (parent-specific) genes that are only expressed from the chromosome of one parent. Considering the more common diseases, epimutations are hatched by various environmental factors resulting in the modulations in the DNA methylation and histone modification patterns as well as altered expression profiles of chromatin-modifying enzymes which turn the healthy cells into malignant phenotype. Most talked game player in the field of cancer is DNA methylation, which if in low levels can cause abnormally increased expression of growth-promoting genes (oncogenes) while its elevated levels reverse the work of protective tumor suppressor genes.
Aforementioned, during embryonic development, commitment of a precursor cell to a more specialized cell occurs in a precise differentiation process, which is driven by a multitude of epigenetic modulations. Chen and Dent (1) summed up the importance of histone methytransferases and deacetylases in post translational modifications required during different stages of cell development and differentiation processes. Mutations in these enzymes have been reported to cause serious disorders including cancers, autoimmune disorders, neurological disorders (Fragile X syndrome, Huntington, Alzheimer, and Parkinson diseases and schizophrenia), making them prime target of researchers in biomedical research and clinical therapy. I have personally contributed to this field by establishing the differentiation of mesenchymal stem cells to cardiac competent cells and also enhancing the numbers of cardiac progenitor cells by employing a histone methytransferase inhibitors in an effort to provide an accessible adult stem cell population for cardiac repair (2,3).
Although science of epigenetics has taken over every laboratory bench space, further research is needed to better understand how epigenetic diseases emanate. Scientific organizations like International Human Epigenome Consortium, are coordinating human epigenomes from different types of normal and disease-related human cell types aiming to determine how the environment and nutrition will modulate epigenetic alterations. Thus, new research data and high-throughput sequencing technologies may help to develop better tools to diagnose patients and provide optimal cell therapies.
1. T. Chen, S.Y.R. Dent. Chromatin modifiers and remodellers: regulators of cellular differentiation. Nat Rev Genet. 2014. 15(2): 93-106.
2. Mezentseva NV,Yang J,Kaur K, Iaffaldano G, Rémond MC, Eisenberg CA, Eisenberg LM. The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells. Stem Cells Dev. 2013;22(4):654-67.
3. Kaur K, Yang J, Edwards JG, Eisenberg CA, Eisenberg LM. G9a histone methyltransferase inhibitor expands adult cardiac progenitor cells without changing their phenotype or differentiation potential. Cell prolif. 2016 Jun;49(3):373-85.
Keerat Kaur is a postdoctoral fellow at Icahn school of Medicine at Mount Sinai in department of cardiology, NY. Her research focuses on reprogramming non-cardiacmyocytes to cardiomyocytes using modified mRNA approach.