Epigenetic Changes

What causes epigenetic changes?

There are different causes for epigenetic changes and Figure 1, shown below, displays some of them as a graphic.

• Aging

• Exercise

• Diet

• Environmental pollutants

• Tobacco usage

• Alcohol

• Stress/Mental health

• Maternal health, diet, and smoking while pregnant

• Environmental weather

• Finances

• Diseases

• Medications

While it can take time, most of these epigenetic changes can be reversed through lifestyle and environmental changes. For example, eating healthier, exercising more, and reducing stress can all help reverse negative epigenetic changes.

Three Mechanisms for Epigenetic Change

There are three main examples of epigenetic changes that can alter gene expression. Fig. 2. shown below shows two of these mechanisms.

DNA methylation uses chemical groups to attach to certain points on the DNA strand. These chemical groups block proteins from attaching to the DNA in order to "read" it. In order to remove the chemical groups, demethylation occurs. Genes are "on" during demethylation and "off" during methylation.

Histone modifications are another example of an epigenetic change. Depending on how close the histones are packed, it determines whether the gene is "off" or "on". Tightly packed histones prevent proteins from binding to the DNA, so it keeps the gene inactivated. Loosely packed histones make the DNA easier for proteins to bind to, so it activates the gene. Chemical groups can be added or removed to alter how tightly or loosely the histones are packed, activating and deactivating the genes.

Examples of Epigenetic Changes

Now, let's explore some examples of epigenetic changes. An example of epigenetics is age. Epigenetics differ from newborn age to childhood and adulthood ages, specifically DNA methylation levels decrease with age.

Another example of epigenetics is how it can be reversible. For example, if someone smokes, then they have decreased levels of DNA methylation compared to someone who does not smoke. If someone quits smoking, it will take time, but their DNA methylation levels will return to the levels of someone who does not smoke.

Epigenetic Changes and Cancer

Epigenetic changes can make organisms more susceptible to illness. For example, some germs can alter epigenetics in order to purposefully weaken the immune system in order to improve their survival within an organism.

Also, during pregnancy, diet plays an important role in the epigenetics of the child and can impact them for decades. For example, if there is a famine, there is less food to eat which can lead to altered levels of DNA methylation for different genes, which can cause possibilities for diseases later on in life such as heart disease or type II diabetes.

Epigenetic changes can also lead to the development of different types of cancers.

Mutations in certain genes can potentially raise the risk for cancer like a mutation in the BRCA1 gene can raise the risk of developing breast cancer. In cancer cells, while certain genes will have high levels of DNA methylation, DNA methylation is overall lower than normal cells. Epigenetics can be used to detect hard-to-find cancers or figure out the certain type of cancer someone has, but more testing will be needed in order to diagnose cancer.

How to Measure Epigenetic Changes

There are multiple different ways to measure epigenetic changes. For example, DNA methylation can be measured using chromatin immunoprecipitation (ChIP) or bisulfite-based methods.

ChIP methods

ChIP methods utilize antibodies that are specifically for methylation to purify the methylated regions in the gene and then the DNA is analyzed using microarrays (example shown below in Fig. 3.)

Bisulfite-based methods

DNA samples are treated with bisulfite in order to assess epigenetic changes. In this method, unmethylated cytosine is transformed into uracil, while methylated bases remain as cytosine.

This method differs from the ChIP method because it can only be used to detect methylation that is sensitive to these bisulfite-based methods. Also, like the ChIP method, the DNA sample will be analyzed using microarrays, but it can also use next-generation sequencing.

For microarray analysis, the bisulfite-based sample is mixed with an untreated sample of DNA, and the ratio of the signal intensity shows the levels of methylation in certain regions of the sample.

When using next-generation sequencing, the bisulfite-treated sample and the untreated sample of DNA are compared to known methylation locations within the gene. In order for this to work, the genome must be well-known. Next-generation sequencing is a three-step process that allows numerous samples to be run together with incredibly fast results.

Differences between genetic and epigenetic changes

There are differences between genetic and epigenetic changes. The main example is that epigenetic changes are from behavior and the environment, while genetic changes are from within the organism. Also, genetic changes involve the DNA sequence, while epigenetic changes do not involve the DNA sequence. Epigenetic changes are also typically considered reversible with changes to lifestyle and environment, and genetic changes are not.

Epigenetic changes and Inheritance

Reproductive cells normally contain epigenetic tags which help determine epigenetic changes, but before reproductive cells are able to meet these tags need to be removed in a process known as reprogramming in order for embryos to create specialized cells as they develop. While most epigenetic tags are removed, a small amount of around 1% is able to sneak through in mammals.