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Most of us recognize the importance of DNA in shaping our bodies. However, in recent years we have come to understand the importance of additional factors in the DNA environment, collectively known as “epigenetics”. These are the factors that make us who we are—that cause a liver cell to differ from a nerve cell—and that account for some of the differences between identical twins.
Darkness, candlelight, and gentle music make an excellent backdrop for one of the defining events of our lives—Dad’s sperm penetrates Mom’s egg, an embryo is formed, and we receive a unique set of DNA that will accompany us for the rest of our lives. You can think of DNA as a “cookbook” that contains the information on how to make all of the proteins required for life: those that accelerate biological processes, those that recognize other molecules in the body, and those that build our body's tissues. Within the DNA “book”, small segments, genes, serve as individual “recipes” that include the instructions for producing a protein.
Although every cell contains the same “cookbook”, each cell receives a unique role (differentiates) and prepares different “dishes”: only pancreatic cells produce the hormone insulin, and only immune cells produce the proteins that comprise antibodies against pathogens. How does each cell know which “recipes” it must prepare and which pages in the “book” will remain closed?
It may surprise you to learn that our DNA is very long. If we were to stretch out a single copy of it—the kind found in almost every cell in our body—we would get a tiny thread about 2 meters (∼6 feet) long (!). For all of this length to fit inside a cell, the DNA is packed in a highly condensed form called a chromosome. The chromosome contains not only the DNA itself but also proteins that help it assume this compact structure, called histones.
But what is the connection to what we mentioned earlier? Naturally, when DNA is condensed, many of its regions are inaccessible to the cellular factors whose job is to read the instructions written in the genes (“read recipes”) and to produce proteins accordingly (“dishes”). Not all DNA regions, however, are condensed to the same extent—some areas are highly compact, whereas others are loose and accessible. Hence, genes located in the relaxed regions are available for “reading” and the proteins they encode are produced, whereas genes located in the condensed regions are not “read” and therefore their proteins are not produced. For example, the DNA segment containing the gene that encodes insulin is free and accessible in pancreatic beta cells, but in all other cells this segment is condensed and inaccessible to the factors that “read the recipe”.
In the 1970s and 1980s several pivotal studies showed how the cell regulates the degree of DNA condensation. It turns out that at any moment cells can add small molecules to the DNA or to the histones (the proteins condensed with it), and these molecules directly affect how tightly the nearby DNA is packed. Some molecules, when added, cause the neighboring DNA to become less condensed and thus the genes in those areas are expressed more, whereas others cause the nearby DNA to become more condensed and thus the genes in those areas are expressed less.
Around the same time the term epigenetics was coined: literally “above genetics”, a term that refers to all the processes that influence gene expression without altering the DNA sequence itself, including the attachment of small molecules to DNA and to histones. Changes in the DNA sequence itself, such as mutations, are permanent—they persist with the cell and with its progeny. In contrast, epigenetic changes—changes in DNA condensation—are not fixed and can vary at different stages of life and in response to environmental changes.
In recent decades it has become clear that epigenetic changes play a crucial role in many bodily processes, for example in embryonic development. The egg cell and the sperm cell are both specialized cells, each with characteristic epigenetic modifications unique to its type. Yet after fertilization they must create a whole embryo, composed of many cell types—not just sperm or egg cells. Therefore, immediately upon fertilization many of the epigenetic modifications of the sperm and egg are “erased”, so that the embryonic cells can develop and turn into various cell types. During development, as cells differentiate into a specific type of cell—for example muscle, liver, or nerve—they acquire epigenetic modifications suited to their role and to the genes they need to express.
Epigenetics also plays a central role throughout adult life. Epigenetic changes occur during normal processes such as puberty, as well as under stress conditions such as severe starvation or disease. A vivid and clear example of epigenetic changes is found in identical twins: even though they share an entirely identical DNA sequence, they display slightly different traits, thanks in part to the epigenetic changes each has undergone over the course of their lifetime.
The 2012 the Nobel Prize in Physiology or Medicine was awarded to Prof. John B. Gurdon and Prof. Shinya Yamanaka, who discovered that the differentiation of cells into various types can be a reversible process and that it can be altered by inducing appropriate epigenetic changes. According to many estimates, this will not be the last Nobel Prize awarded for epigenetics research—two leading candidates for the prize are Prof. Aharon Razin and Prof. Chaim Cedar of the Hebrew University, whose discoveries have greatly influenced medical research and cancer research in particular.
English editing: Elee Shimshoni
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