Epigenetics is the relatively new study of the biological mechanisms that result in inheritable changes in the control of genes but do not involve any changes in the sequence of DNA base pairs.
By studying epigenetics, researchers hope to better understand how the environment—everything from exposure to chemicals to diet to early traumatic experiences—affects gene expression. With a better understanding of how these influences turn on and turn off genes, they hope to explain why some people respond to drugs and treatments while others with the same disease do not, with the eventual goal of developing more personalized medicine.
Deoxyribonucleic acid (DNA) is a double helix made up of long sequences of four paired compounds called nucleotide bases. These bases make up about 20,000 genes in humans. The order in which the bases occur provides instructions for making proteins that control all the body's biological functions as well as its external appearance. Changes in nucleotide bases are called mutations. These changes are inherited, and they account for many, but not all, differences among individuals.
The field of epigenetics examines changes at the molecular level that affect gene expression—that is, changes that either turn on or turn off gene functions—and can be inherited but that do not involve nucleotide base changes (mutations). These epigenetic changes are the result of interactions with the environment, and they differ from person to person, so that on an epigenetic level, even monozygous (identical) twins, whose DNA is the same, are not biochemically identical.
Epigenetic factors play a role in normal development. They explain how stem cells that have identical DNA can differentiate into many different specialized cells. For example, stem cells in bone marrow differentiate into red blood cells, platelets, and a dozen or more different kinds of white blood cells, all with different functions, even though their DNA base sequence is identical. Muscle cells are different from skin cells; liver cells are different from brain cells. All this happens during normal development because genes are turned on and off by epigenetic factors that provide additional information that overlays the basic information found in DNA. In addition, epigenetic changes, unlike mutations, are reversible. They may cause a gene to produce a specific protein at one stage of life but not at another. For example, young children do not produce many sex hormones. The genes that control their production are turned off. Then just before puberty, those genes are turned on. They continue to function during early and middle adulthood and gradually turn off in old age.
Just as epigenetic factors can turn on and off genes necessary for normal development, they can also turn on and off genes that lead to abnormal development or disease. For example, researchers have identified a group of genes called tumor suppressor genes. If these genes are turned off, then cancer cells can grow unchecked. There are also genes responsible for making proteins that repair damaged DNA. If these are turned off, then unrepaired DNA damage may cause disorders or abnormalities of development. However, the fact that epigenetic changes are reversible suggests that researchers may find ways to prevent or treat diseases by reversing the epigenetic effect.
As of 2018, epigenetic changes were known to occur through three mechanisms. The first is through methylation of DNA. A methyl group contains one carbon (C) atom bonded to three hydrogen (H) atoms. When methyl groups attach to DNA, the process is called DNA methylation. Methylation and demethylation (removal of a methyl group) appear to affect whether and to what degree a gene is turned on or off.
The second way information can be overlaid on basic DNA information is through the attachment of methyl groups and other small molecules to histone proteins. Histone proteins are closely associated with DNA and affect the shape it takes. The attachment of small molecules to histones can change the shape of the DNA-histone complex and either open up sections of the DNA making it more accessible and thus turning it on or make the DNA-histone complex tighter, thus shutting down the function of certain sections of DNA.
A third way epigenetic factors can affect cell functions is through interactions with ribonucleic acid (RNA), a protein that is a critical intermediary between the instructions in the DNA and formation of functioning proteins.
Epigenetic factors are thought to be related to lifestyle and environmental exposures and believed to be passed from parent to child. In one famous experiment, researchers mated a pair of agouti mice. Agouti mice carry a gene that makes them ravenous eaters with yellow fur and a predisposition to develop cancer and diabetes. Normally a pair of agouti mice will produce fat, yellow agouti offspring.
In this case, the researchers wanted to see if they could change this inheritance pattern by using lifestyle factors. Before the female was bred, the researchers fed her a diet high in methyl compounds. These are compounds that attach to DNA and turn genes off. The result was a litter of slim, brown mice that were not predisposed to cancer or diabetes. The DNA had not changed; the offspring still had the agouti gene, but the methyl groups in the mother's food appeared to have attached to the DNA of that gene and turned it off. In other words, the researchers changed the phenotype (appearance) of the offspring without changing the genotype.
Other research has shown that different environmental experiences, such as starvation, can cause epigenetic changes that can be passed on for several generations. The field of epigenetics is relatively new and rapidly expanding. The agouti mouse experiment was performed in 2000. However, it appears that early lifestyle factors and environmental exposures such as exposure to atmospheric pollution can alter the tags on DNA and turn on or off certain genes in ways that could be related to disease, while certain vitamins and nutrients may protect against this. The phenomenon appears less pronounced in adults than in children and may even be more pronounced on fetuses in the womb.
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Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, United Kingdom, +44 0 1223 496000, https://www.babraham.ac.uk .
Cancer Epigenetics Society, Wergertorgasse 12/2/6, Vienna, 1010, Austria, +43 123 13-985, email@example.com, https://ces.b2sg.org .
Memorial Sloan Kettering Cancer Center for Epigenetics Research, 1275 York Ave., New York, NY, 10065, (212) 63902000, https://www.mskcc.org/research-programs/epigenetics-research .
National Cancer Institute, BG 9609 MSC 9760, 9609 Medical Center Dr., Bethesda, MD, 20892-9760, (800) 332-8615, http://www.cancer.gov .
Revised by Tish Davidson, AM