Have you ever thought about how we have many kinds of different cell types while we have just one genome? If all our cells have the same DNA sequence, how come we have blood cells, neural cells, skin cells and so on? Can we change our destiny on behalf of the diseases even if just a drop? If we are a person who smokes cigarettes, using drugs, drinking too much alcohol; could these awful habits affect even our grandchild? In fact, even your financial situation can modify your genes. The phenomenon that is responsible for all these astonishing facts is called epigenetics that means “on top of genetics”. Basically, it is the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence.
In the early years of (epi)genetics, the main questions were: What molecules within the chromosomes carried the genetic information, how did they manage the developmental program, and how was the information transmitted during cell division? It was understood that both nucleic acid and proteins were present in chromosomes, but their relative contributions were not obvious. After the discovery of central dogma modern biology emerged. This dogma covers the processes involved in maintaining and translating the genetic template required for life and now we know, epigenetics can interfere with the steps of the central dogma.
If we want to explain the term of epigenetic more detailed, at first, we could say DNA is not “naked” in organisms. Instead, it forms chromatin with some specialized proteins. The primary protein components of chromatin are histones, which bind to DNA and function as "anchors" around which the strands are bound. Chromatin was initially only regarded as a passive packaging molecule to wrap and organize the DNA. After, we realized that chromatin structure is also important for regulation of gene expression. Certainly, after the packaging of DNA to better fit into a confined space, also a problem develops, much as when packs too many books onto library shelves: It becomes harder to find and read the book of choice. Therefore, an indexing system is needed. Which is why, chromatin, as a genome-organizing platform, provides this indexing.
The DNA sequence of our genome is formed of about 3x109 bases. These bases are A, C, G, and T constitute to well-defined words, namely genes, in the sequence. Among these "well-defined words"; there are some regions that are responsible for suppressing or enhancing the transcription, some starting points (promoters), binding sites of some special proteins, coding or non-coding parts and so on. Before the RNA polymerase which is the main transcription enzyme responsible for the initiation of the gene expression reaches the promoter, this part for the DNA must be accessible. At this point, some different mechanisms come into play such as the binding of a transcription factor, remodeling complex recruitments, special histone modifications, and some histone variants. Via these factors, chromatin can be in two different forms; euchromatin and heterochromatin. While euchromatin is lightly packed and transcriptionally active, heterochromatin can broadly be defined as highly compacted and silenced. Every single cell in our body have their own epigenome and their chromatin structures are also different that is why they have different levels of transcription of genes.
All the genetic concepts as we mentioned can be affected by our lifestyle. Maybe the best example for seeing this is monozygotic twins who have the same DNA. In their childhoods, they seem similar and even nearly the same. But with the passing of time their appearance change as enough as can distinguish them from each other. One of them could be fit and well while the other one obese and unhealthy because of eating fast foods, smoking and not doing sports. One study via Chromosome Analysis Assay showed us that the 50-year old twins have more epigenetic tags in different places than 3-year-old twins. This sample shows us the importance of habits and environment in our lives.
If you think your habits could only affect yourself, you are wrong. A study on rats suggested that eating poorly during pregnancy can increase your children's and your grandchildren's risk of cancer. Even if they themselves eat healthily! Researcher Rod Dashwood of Oregon State University said, "People think there is nothing you can do about your disease risk, but you are not just what your genes."
What about are not there any hope for you too if you are a junkie? Of course, there is. On the contrary of DNA mutations, we know that the epigenetic changes are reversible! So, it means that if you change your habits such as diet, your epigenome can get better. The feature of being reversible mainly depends on reading, erasing or writing of some epigenetic marks. That epigenetic marks may provide “ON” (i.e., active) or “OFF” (inactive) signatures. All these dynamic and complex processes hold on in our cells in all time. For example, while a reader is reading a mark such as methylation, also an eraser would erase the mark of acetylation and these would cause a suppression of the related gene. At this time, writers could bring new methylation markers to the histone tails or DNA. So, you would better believe it you can change your genes destiny! For instance, some studies showed green tea polyphenols can decrease cancer risk via inhibition of DNA methylation.
Up to now, we have mentioned some of the effects of epigenetics on transcription. But there is something more; non-coding RNAs. These RNAs can effect on translation because they are post-transcriptional modulators. Till about thirty years ago, we had been using the terms of "junk" DNA to the regions that do not code proteins. Miraculously we had realized that these regions are actually really important for our gene expression regulation. Then, the term "non-functional" turned into "non-coding". Amazingly, almost 99% of the human genome is non-coding and these regions include RNAs involved in protein synthesis, post-transcriptional modifications, DNA replication and control of gene expression. One of the examples of these regulatory RNAs is microRNA, a major category among the noncoding RNAs that negatively regulate expression by either degrading the target messages or inhibiting their translation. During aging, predominantly up-regulated miRNA expression is observed, and this causes a decrease of protein levels. In addition to this, genomic hypomethylation is also observed in both aging and cancer. All this would cause something to go wrong.
To sum up, your genes do not determine everything for you. Hard to believe; but not only your diet, exercise, toxic chemicals that imposed or drugs you use but also social interactions, microbiome, psychological state, weather conditions and so on could change your epigenome! As a result, having "good genes" is not enough for neither ourselves, nor for the healthy development of our children, but we should also "keep healthy" our own DNA for these. When the next time someone says you "Friend, you should not smoke any longer", please think about your future grandchild.
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