Epigenomics Fact Sheet

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


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What is the epigenome?

A genome is the complete set of deoxyribonucleic acid, or DNA, in a cell. DNA carries the instructions for building all of the proteins that make each living creature unique.

Derived from the Greek, epigenome means "above" the genome. The epigenome consists of chemical compounds that modify, or mark, the genome in a way that tells it what to do, where to do it and when to do it. The marks, which are not part of the DNA itself, can be passed on from cell to cell as cells divide, and from one generation to the next.

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What does the epigenome do?

Each person's body contains trillions of cells, all of which have essentially the same genome. Yet some cells are optimized for use in muscles, others for bones, the brain, the stomach and the rest of your body. What makes these cells different?

The protein-coding parts of your genome, called genes, do not make proteins all of the time in all of your cells. Instead, different sets of genes are turned on or off in various kinds of cells at different points in time. Differences in the types and amounts of proteins produced determine how cells look, grow and act. The epigenome influences which genes are active - and which proteins are produced - in a particular cell.

So, the epigenome is what tells your skin cells to behave like skin cells, heart cells like heart cells and so on.

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What makes up the epigenome?

The epigenome is made up of chemical compounds, some of which come from natural sources like food and others from man-made sources like medicines or pesticides. As it marks the genome with these chemical tags, the epigenome serves as the intersection between the genome and the environment.

The epigenome marks your genome in two main ways, both of which play a role in turning genes off or on.

The first type of mark, called DNA methylation, directly affects the DNA in your genome. In this process, chemical tags called methyl groups attach to the backbone of the DNA molecule in specific places. The methyl groups turn genes off or on by affecting interactions between DNA and the cell's protein-making machinery.

The second kind of mark, called histone modification, indirectly affects the DNA in your genome. Histones are spool-like proteins that enable DNA's very long molecules to be wound up neatly into chromosomes inside the cell nucleus. A variety of chemical tags can grab hold of the tails of histones, changing how tightly or loosely they package DNA. If the wrapping is tight, a gene may be hidden from the cell's protein-making machinery, and consequently be switched off. In contrast, if the wrapping is loosened, a gene that was formerly hidden may be turned on.

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Is the epigenome inherited?

Just as the genome is passed along from parents to their offspring, the epigenome can also be inherited. The chemical tags found on the DNA and histones of eggs and sperm can be conveyed to the next generation.

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What is imprinting?

Your genome contains two copies of every gene - one inherited from your mother and one from your father. For some genes, only the copy from the mother ever gets switched on, and for others, only the copy from the father. This pattern is called imprinting.

The epigenome serves to distinguish between the two copies of an imprinted gene. For example, only the father's copy of a gene called IGF2 is able to make its protein. That is because marks in the epigenome keep the mother's IGF2 copy switched off in every cell of the body.

Some diseases are caused by abnormal imprinting. They include Beckwith-Wiedmann syndrome, a disorder associated with body overgrowth and increased risk of cancer; and Prader-Willi and Angelman syndromes, which are disorders associated with obesity and mental retardation.

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Can the epigenome change?

While all cells in your body contain essentially the same genome, the chemical tags on the DNA and histones get rearranged in different cell types. The epigenome can also change throughout a person's lifetime.

Consider the case of identical twins. Although they share nearly the same genome, their bodies may not be exactly identical. One twin may weigh more, for example, or develop arthritis. Researchers think that at least some of these differences are due to changes in the epigenome.

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What makes the epigenome change?

Lifestyle and environmental factors can expose a person to chemical tags that change the epigenome. In other words, your epigenome may change based on what you eat and drink, whether you smoke, what medicines you take, what pollutants you encounter and even how quickly your body ages. There is also some evidence from animal and human studies that indicates that what a female eats and drinks during pregnancy may change the epigenome of her offspring.

Most epigenomic changes are probably harmless, but some changes may trigger or increase the severity of disease. Researchers already have linked changes in the epigenome to various cancers, diabetes, autoimmune diseases and mental illnesses.

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How do changes in the epigenome contribute to cancer?

Cancers are caused by a combination of changes to the genome and the epigenome.

Adding or removing methyl groups can switch genes involved in cell growth off or on. If such changes occur at the wrong time or in the wrong cell, they can wreak havoc, converting normal cells into cancer cells that grow wildly out of control.

For example, in a type of brain tumor called glioblastoma, doctors have had some success in treating patients with a drug, called temozolomide, that kills cancer cells by adding methyl groups to DNA. But that's only part of a very complex picture. Cells also contain a gene, called MGMT, that produces a protein that subtracts methyl groups - an action that counteracts the effects of temozolomide. In some glioblastomas, however, the switch for the MGMT gene has itself been turned off by methylation, which blocks production of the protein that counteracts temozolomide. Consequently, glioblastoma patients whose tumors have methylated MGMT genes are far more likely to respond to temozolomide than those with unmethylated MGMT genes.

Changes in the epigenome also activate growth-promoting genes in stomach cancer, colon cancer and the most common type of kidney cancer. In other cancers, changes in the epigenome silence genes that normally serve to keep cell growth in check.

To come up with a complete list of all the possible changes that can lead to cancer, the National Institutes of Health (NIH) has started a project called The Cancer Genome Atlas. Beginning with glioblastoma, these researchers are comparing the genomes and epigenomes of normal cells to those of cancer cells. They are looking for any changes in the DNA sequence, called mutations; changes in the number and structure of chromosomes; changes in the amounts of proteins produced by genes; and changes in the number of methyl groups on the DNA.

Understanding all the changes that turn a normal cell into a cancer cell will speed efforts to develop new and better ways of diagnosing, treating and preventing cancer. To learn more about this effort, go to http://cancergenome.nih.gov.

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How are researchers exploring the epigenome?

Researchers are exploring the epigenome through a field called epigenomics, which is the study of all the chemical tags on the genome that control the activities of genes. This is different from genomics, which is the study of all the changes that occur in the order, or sequence, of the DNA building blocks that make up the genome.

Experts once thought that diseases were caused mainly by changes, or mutations, in DNA sequence - changes that either disrupt protein production or lead to abnormal proteins. Recently, researchers have learned that changes in the epigenome may cause or contribute to many diseases, making epigenomics a vital part of efforts to better understand the human body and improve human health.

As part of its Roadmap for Medical Research, the NIH plans to develop a map of the epigenomic marks that occur on the human genome. The effort will require the development of better technologies to quickly and efficiently detect epigenomic marks, as well as improved understanding of the factors that drive these changes. To learn more about this effort, go to http://commonfund.nih.gov/epigenomics.

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Last Updated: February 9, 2015