What is Epigenetics?

figure pointing at a double helix

Your genes play an important role in your health, but so do your behaviors and environment, such as what you eat and how physically active you are. Epigenetics is the study of how your behaviors and environment can cause changes that affect the way your genes work. Unlike genetic changes, epigenetic changes are reversible and do not change your DNA sequence, but they can change how your body reads a DNA sequence.

Gene expression refers to how often or when proteins are created from the instructions within your genes. While genetic changes can alter which protein is made, epigenetic changes affect gene expression to turn genes “on” and “off.” Since your environment and behaviors, such as diet and exercise, can result in epigenetic changes, it is easy to see the connection between your genes and your behaviors and environment.

How Does Epigenetics Work?

Epigenetic changes affect gene expression in different ways. Types of epigenetic changes include:

DNA Methylation

DNA methylation works by adding a chemical group to DNA. Typically, this group is added to specific places on the DNA, where it blocks the proteins that attach to DNA to “read” the gene. This chemical group can be removed through a process called demethylation. Typically, methylation turns genes “off” and demethylation turns genes “on.”

Histone modification

DNA wraps around proteins called histones. When histones are tightly packed together, proteins that ‘read’ the gene cannot access the DNA as easily, so the gene is turned “off.” When histones are loosely packed, more DNA is exposed or not wrapped around a histone and can be accessed by proteins that ‘read’ the gene, so the gene is turned “on.” Chemical groups can be added or removed from histones to make the histones more tightly or loosely packed, turning genes “off” or “on.”

Non-coding RNA

Your DNA is used as instructions for making coding and non-coding RNA. Coding RNA is used to make proteins. Non-coding RNA helps control gene expression by attaching to coding RNA, along with certain proteins, to break down the coding RNA so that it cannot be used to make proteins. Non-coding RNA may also recruit proteins to modify histones to turn genes “on” or “off.”

How Can Your Epigenetics Change?

Your epigenetics change as you age, both as part of normal development and aging and in response to your behaviors and environment.

  1. Epigenetics and Development
    Epigenetic changes begin before you are born. All your cells have the same genes but look and act differently. As you grow and develop, epigenetics helps determine which function a cell will have, for example, whether it will become a heart cell, nerve cell, or skin cell.
Example: Nerve cell vs. Muscle cell

Your muscle cells and nerve cells have the same DNA but work differently. A nerve cell transports information to other cells in your body. A muscle cell has a structure that aids in your body’s ability to move. Epigenetics allows the muscle cell to turn “on” genes to make proteins important for its job and turn “off” genes important for a nerve cell’s job.

  1. Epigenetics and Age
    Your epigenetics change throughout your life. Your epigenetics at birth is not the same as your epigenetics during childhood or adulthood.
Example: Study of newborn vs. 26-year-old vs. 103-year-old

DNA methylation at millions of sites were measured in a newborn, 26-year-old, and 103-year-old. The level of DNA methylation decreases with age. A newborn had the highest DNA methylation, the 103-year-old had the lowest DNA methylation, and the 26-year-old had a DNA methylation level between the newborn and 103-year-old (1).

  1. Epigenetics and Reversibility
    Not all epigenetic changes are permanent. Some epigenetic changes can be added or removed in response to changes in behavior or environment.
Example: Smokers vs. non-smokers vs. former smokers

Smoking can result in epigenetic changes. For example, at certain parts of the AHRR gene, smokers tend to have less DNA methylation than non-smokers. The difference is greater for heavy smokers and long-term smokers. After quitting smoking, former smokers can begin to have increased DNA methylation at this gene. Eventually, they can reach levels similar to those of non-smokers. In some cases, this can happen in under a year, but the length of time depends on how long and how much someone smoked before quitting (2).

Epigenetics and Health

Epigenetic changes can affect your health in different ways:

  1. Infections
    Germs can change your epigenetics to weaken your immune system. This helps the germ survive.
Example: Mycobacterium tuberculosis

Mycobacterium tuberculosis causes tuberculosis. Infections with these germs can cause changes to histones in some of your immune cells that result in turning “off” the IL-12B gene. Turning “off” the IL-12B gene weakens your immune system and improves the survival of Mycobacterium tuberculosis (3).

  1. Cancer
    Certain mutations make you more likely to develop cancer. Likewise, some epigenetic changes increase your cancer risk. For example, having a mutation in the BRCA1 gene that prevents it from working properly makes you more likely to get breast and other cancers. Similarly, increased DNA methylation that results in decreased BRCA1 gene expression raises your risk for breast and other cancers (4).While cancer cells have increased DNA methylation at certain genes, overall DNA methylation levels are lower in cancer cells compared with normal cells. Different types of cancer that look alike can have different DNA methylation patterns. Epigenetics can be used to help determine which type of cancer a person has or can help to find hard to detect cancers earlier. Epigenetics alone cannot diagnose cancer, and cancers would need to be confirmed with further screening tests.
Example: Colorectal Cancer

Colorectal cancers have abnormal methylation at DNA regions near certain genes, which affects expression of these genes. Some commercial colorectal cancer screening tests use stool samples to look for abnormal DNA methylation levels at one or more of these DNA regions. It is important to know that if the test result is positive or abnormal, a colonoscopy test is needed to complete the screening process (5).

  1. Nutrition During Pregnancy
    A pregnant woman’s environment and behavior during pregnancy, such as whether she eats healthy food, can change the baby’s epigenetics. Some of these changes can remain for decades and might make the child more likely to get certain diseases.
Example: Dutch Hunger Winter Famine (1944-1945)

People whose mothers were pregnant with them during the famine were more likely to develop certain diseases such as heart disease, schizophrenia, and type 2 diabetes (6). Around 60 years after the famine, researchers looked at methylation levels in people whose mothers were pregnant with them during the famine. These people had increased methylation at some genes and decreased methylation at other genes compared with their siblings who were not exposed to famine before their birth (7)(8)(9). These differences in methylation could help explain why these people had an increased likelihood for certain diseases later in life (6)(9)(10)(11).

More Information
  1. Heyn H, Li N, Ferreira H, et al., Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A 2012; 109:10522-7
  2. McCartney D, Stevenson A, Hillary R, et al., Epigenetic signatures of starting and stopping smoking. EBioMedicine 2018; 37:214-220
  3. Chandran A, Antony C, Jose L, et al., Mycobacterium Tuberculosis Infection Induces HDAC1-Medicated Suppression of IL-12B Gene Expression in Macrophages. Front Cell Infect Microbiol 2015; 5:90.
  4. Tang Q, Cheng J, Cao X, et al., Blood-based DNA methylation as biomarker for breast cancer: a systematic review. Clin Epigenetics 2016; 8: 115.
  5. Chan SCH, Liang JQ. Advances in tests for colorectal cancer screening and diagnosis. Expert Rev Mol Diagn 2022; 22: 449-460.
  6. Roseboom T., Epidemiological evidence for the developmental origins of health and disease: effects of prenatal undernutrition in humans. J Endocrinol 2019. 242:T135-T144
  7. Heijmans B, Tobi E, Stein A, et al., Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 2008; 105: 17046-17049.
  8. Tobi E, Lumey L, Talens R, et al., DNA Methylation Differences After Exposure to Prenatal Famine Are Common and Timing- And Sex- Specific. Hum Mol Genet 2009; 18:4046-53.
  9. Tobi E, Slieker R, Luijk R, et al., DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood. Sci Adv 2018; 4:eaao4364.
  10. Dayeh T, Tuomi T, Almgren P, et al., DNA Methylation of Loci Within ABCG1 and PHOSPHO1 in Blood DNA is Associated With Future Type 2 Diabetes Risk. Epigenetics 2016; 7: 482-8.
  11. Pidsley R, Dempster E, Troakes C, et al., Epigenetic and genetic variation at the IGF2/H19 imprinting control region on 11p15.5 is associated with cerebellum weight. Epigenetics 2012; 7:155-163.