Epigenetics

The term epigenetics is used to describe the changes in the characteristics of a cell or an organism that are not due to
changes in the nucleotide sequence of the DNA. Epigenetics refers to how your behaviors and environment can cause
changes that affect the way your genes work. Unlike genetic changes (mutations), epigenetic changes are reversible
and do not change the sequence of DNA bases, but they can change how your body reads a DNA sequence.

While changes to the genes (mutations) can change the protein that is made, epigenetic changes affect gene
expression to turn genes "on" and "off." This can mean that genes make proteins in cells and tissues where or when
they normally would not, or that genes don't make proteins where and when they normally would. It can also mean
that genes make more or less of a protein than they normally would.

There are several ways an environmental factor can cause an epigenetic change to occur. One of the most common
ways is by causing changes to DNA methylation. DNA methylation works by adding a chemical (known as a methyl
group) to DNA. This chemical can also be removed from the DNA through a process called demethylation. Typically,
methylation turns genes off and demethylation turns genes on. Thus, environmental factors can impact the amount
of protein a cell makes. Less protein might be made if an environmental factor causes an increase in DNA
methylation, and more protein might be made if a factor causes an increase in demethylation.

Histone Modification

DNA is wrapped around histone proteins to form chromatin, which can be either loosely packed (euchromatin) or
tightly packed (heterochromatin).

• Loosely packed chromatin (euchromatin):

o More DNA is exposed and accessible.

o Allows transcription factors and RNA polymerase to bind easily.

o Genes in euchromatin are usually active (expressed).

o Example: Histone acetylation (adding acetyl groups) reduces the positive charge on histones,
loosening chromatin and promoting gene transcription.

• Tightly packed chromatin (heterochromatin):

o DNA is less exposed and harder to access.

o Prevents transcription machinery from binding.

o Genes in heterochromatin are usually silent (repressed).

o Example: Histone methylation can tighten chromatin, leading to gene silencing.

Non-Coding RNA (ncRNA)

Non-coding RNAs help control gene expression by interacting with coding RNA (mRNA) to regulate its function.

• MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) attach to mRNA, blocking its translation or
marking it for degradation.

• Long non-coding RNAs (lncRNAs) can bind to mRNA or proteins, influencing gene activation or repression.

• Piwi-interacting RNAs (piRNAs) help silence transposable elements, protecting genome stability.

Example: miR-21 binds to tumor suppressor mRNA and prevents its translation, leading to uncontrolled cell
growth in cancer.
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, muscle cell, or skin cell.

EXAMPLE: Nerve cell and muscle cell. Your nerve cells and muscle cells have the same DNA, but they 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.

Epigenetics and age

Your epigenetics change throughout your life. Your epigenetics at birth are not the same as your epigenetics during
childhood or adulthood.

EXAMPLE: A newborn, 26-year-old, and 103-year-old. Scientists measured DNA methylation at millions of sites in a
newborn, 26-year-old, and 103-year-old. The level of DNA methylation decreased with age. The newborn had the
highest level of DNA methylation, the 103-year-old had the lowest level of DNA methylation, and the 26-year-old had
a DNA methylation level that was between that of the newborn and the 103-year-old.1

Epigenetics and exposures

Your epigenetics can change in response to your behaviors and environment.

Nutrition during pregnancy

A pregnant woman's environment and behavior during pregnancy, such as whether they eat 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.2 Around 60 years after the famine, researchers looked at DNA methylation levels in people whose mothers
were pregnant with them during the famine. These people had increased DNA methylation at some genes and
decreased DNA methylation at other genes, compared with their siblings who were not exposed to famine before
birth. 345These differences in DNA methylation could help explain why these people had an increased likelihood for
certain diseases later in life.2567

Smoking

Exposures such as smoking can cause epigenetic changes. However, these epigenetic changes can be reversible in
some cases.

EXAMPLE: Smokers, nonsmokers, and 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 nonsmokers. 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 nonsmokers. In some
cases, this can happen in less than a year, but the length of time depends on how long and how much someone
smoked before quitting.8

Epigenetics and diseases

Certain diseases can change your epigenetics. In addition, some epigenetic changes can make you more likely to
develop certain diseases, such as cancer.

Infections

Germs can change your epigenetics to weaken your immune system. This helps the germ survive.
EXAMPLE: Tuberculosis. Mycobacterium tuberculosis causes tuberculosis. Infections with these germs can cause
epigenetic changes 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.9

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.10 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 seem similar 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. Cancers would need to be confirmed with further screening tests.

EXAMPLE: Colorectal cancer. Colorectal cancers have abnormal DNA methylation near certain genes, which affects
expression of these genes.