The Epigenetics Revolution: How Modern Biology is Rewriting Our Understanding of Genetics, Disease and Inheritance

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If our DNA is the script for our play, epigenetic modifications act as a multitude of varied performances, enabling our cells - which, again, all have identical DNA - to specialise in completely different ways. This is why we don't have teeth in our eyes, for example. Carey guides us through detailed descriptions about how the genome is regulated through various methods, such as methylation, acetylation, histone changes, and most remarkably, the way that DNA codes non-coding RNA, which in turn regulates DNA. DNA itself creates RNA molecules that act like dial-turners or button pushers, augmenting or reducing DNA expression. Only two percent of the human genome codes for the manufacture of protein. “The fact that ninety-eight percent of the human genome does not code for protein suggests that there has been a huge evolutionary investment in the development of complicated non-coding RNA-mediated regulatory processes…Complicated networks of molecules influence how, when and to what degree proteins are expressed.” What regulates the gene expressions in many of the biological processes are the epigenetic mechanisms. The idea of inheritance, adopted by the majority of people, is that the genes and environment act together in producing the characteristics of an organism. Research on the epigenetic inheritance of addictive behavior is less advanced, but does look quite promising. Studies in rats recently demonstrated that exposure to THC (the active compound in cannabis) during adolescence can prime future offspring to display signs of predisposition to heroin addiction.

This book is more interesting than pleasant, more arduous than easy, and it is not for the average reader, but I constantly felt like cheering for the excellence of Nessa Carey who is so determined to bring to our attention the wonder of genetic inventiveness within our life. The last part of the book gives insight into how epigenetic mechanisms can contribute to the errors in cell division and differentiation, which can cause various human diseases, such as cancer. Being one of the best-rated epigenetics books, this one is a great resource for everyone interested in the field. This is a field that’s guaranteed to keep generating headlines and catching the public’s interest. The apparent ability of epigenetics to fill some pretty diverse gaps in our understanding of human health and disease, and to provide scientific mechanisms for so many of our lived experiences, makes it very compelling, but we do need to be careful not to over-interpret the evidence we’ve collected so far. And we certainly need to be highly sceptical of anyone claiming that we can consciously change our epigenomes in specific ways through the power of thought.

For deeply historical reasons, our genes are first transcribed into a chemical, RNA, which is eventually translated into proteins, which then do pretty much all the work of making and caring for our bodies. Mutations in genes over time produce changes in the proteome (the set of proteins that make up a body), which results in different creatures. But now we know that there's more to the story. Chemical markers that are attached to genes, and which often end up there as a result of things experienced during a lifetime, can dramatically alter how genes are expressed. As an example, when a child is raised in a stressful environment, epigenetic changes may cause the child to more readily produce stress-related hormones, and those epigenetic changes may last throughout the person's lifetime. Even under low stress situations, that same child may produce more of the harmful stress hormones as an adult. Bisphenol A (BPA) is an additive in some plastics that has been linked to cancer and other diseases and has already been removed from consumer products in some countries. BPA seems to exert its effects through a number of mechanisms, including epigenetic modification.

As the book unfolds into the later chapters, the subject of epigenetic gene regulation of cancer cells is by far the most fascinating subject of this book. Everything in the first part of the book will lead you to the understanding of this topic. For a long time now, the study of cancer has solely focused on mutations of specific genes that appear to be located in cancer tumors. Later, in more recent years, cancer research has been aimed at epigenetic therapy, and as a result research on epigenetic gene regulation of cancer tumor cells. For me, one of the most interesting parts of the book was the explanation of how your environment growing up, as well as your genetics, both influence mental health. This was particularly fascinating as it shows how epigenetics, which seems like a very niche subject, is relevant to people in their day to day lives. It also made me think a lot more about the genetics I was learning about in school, and how it can all be ultimately applied to real people.

Contents

Epigenetics – a relatively new sub-field in genetics that has been developing fast since scientists realized that our genetic expressions can change under the influence of various environmental factors. The change we may experience isn’t only on a psychological level, but on a cellular, genetic level. The difference between genetics and epigenetics is that epigenetic changes are reversible and don’t exactly change the DNA sequence. Instead, they have an effect on how our body reads the affected DNA sequences. How Do Our Epigenetics Change? Three different epigenetic mechanisms have been identified: DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing. Catalyzed by DNA methyltransferase enzymes, DNA methylation involves the addition of a methyl group directly to a cytosine nucleotide within a cytosine-guanine sequence (CpG), which are often surrounded by other CpG’s forming a CpG island. CpG islands are common targets for epigenetic DNA methylation, notably the CpG islands within promoter regions. Indeed, it has been reported that around 70% of gene promotor regions lie within CpG islands. [13] Methylated cytosines within a promoter region recruit gene suppressor proteins and reduce interaction between the DNA and transcription factors. [14] Cytosine methylation also drives the formation of heterochromatin, so the nucleosome tightening prevents transcriptional machinery from interacting with the DNA. [15] As such, DNA methylation within promoter regions results in gene silencing. Cancers often show marked hypermethylation of tumor suppressor genes and hypomethylation of proto-oncogenes, both of which contribute to tumor carcinogenesis. [15] This epigenetic mechanism also plays an important role in tissue-specific gene regulation, genomic imprinting, and X chromosome inactivation. [14] Perhaps the most studied clinical application of epigenetic mechanisms is cancer. One of the first reports of epigenetics involved in cancer reported hypomethylation of DNA in cancer cell genomes, which caused overexpression of genes within that cell. [26] Since this report, great strides have been made toward understanding the role of epigenetics in carcinogenesis. For example, the degree of DNA methylation continues to decrease as a benign tumor cell progresses to invasive cancer. [27] Other studies have shown hypomethylation of pro-proliferative genes like BAX2 that are suppressed in normal cells. [28] Other reports show hypermethylation of tumor suppressor genes, like Rb, BCRA1, and CDKN2A, in cancer cells. [29] [30] [31]Despite the wealth of knowledge present on the relationship between epigenetics and carcinogenesis, treatment development is still very much in the preliminary phase formost cancers. Reading this was a brilliant journey; there were parts I found a little slow but in the majority I found it interesting. Carey touched on a bit of everything, not only showing how much epigenetics shape us but it avoided the book becoming a drag.