Histone modifications

The structure of DNA is a double helix, something many of us will remember from our high school biology class, a discovery made by Watson and Crick by borrowing data from others (like Rosalind Franklin). In reality, the form that DNA is found in when it is inside the cell of a living organism is much more complicated than the double helix. DNA is wound and bunched and then condensed into much larger structures called chromosomes. It is the components that make up these chromosomes that play key roles in epigenetics and controlling gene activity.

The DNA that is found in our cells, and in the cells of most living organisms, is associated with proteins called histones. This complex of DNA and protein is called “chromatin.”

The primary reason that the DNA wraps around these proteins is to fit inside our cells. If our DNA were not condensed, one chromosome would measure roughly 5 centimeters long—the length from my ring finger knuckle to the end of my nail—and that’s just one of them! There’s another 45 (23 pairs) that would need to fit into each cell too! It is because of the organization around histone proteins that DNA can fit inside our cells.

However, the winding of DNA around histones is not solely to allow our DNA to fit into a small space. There are many factors that contribute to how tightly the chromatin is wound. When histone proteins are modified, it results in a change in the chromatin structure. There are several histone modifications known to date, the most well-known include: acetylation, methylation, phosphorylation, ubiquitylation, SUMOylation, and biotinylation.

Whether these histone “tags” as they are called, are attached to histones or not is what dictates the tightness or looseness of the chromatin structure. In general, tight winding (called heterochromatin) results in lower expression of local genes due to its compact state and loosely wound DNA (called euchromatin) results in higher expression of local genes because the DNA is open and available to the expression machinery.

Enzymes in the cell perform the addition or removal of histone tags. Acetylation and methylation are the most common tags that are placed onto histone proteins. A family of at least 20 enzymes called histone acetyltransferases (HATs) is responsible for the process of acetylation. The enzymes that remove acetyl groups are called histone deacetylases (HDACs).

The effect of histone modifications results from the sum of many different modifications occurring at once, rather than a single tag in isolation. This complicated process is referred to as the “histone code.”

There is still an active debate to the degree of which histone modifications are an epigenetic process. Some evidence has suggested that environmental triggers (like diet or stress) can influence the arrangement of histones. It is also possible that some of these modifications may be passed onto to the next generation, however, no mechanism has been proposed for how this could occur and the idea is controversial in the scientific community.