Basics of Epigenetics

Historically, the definition of epigenetic was a bit different than how the term is now used. In genetics today epigenetics refers to chemical modifications of DNA (excluding changes in the nucleotide sequence), or of the structural or regulatory proteins that are associated with DNA. These modifications can be transient or they can be maintained through many cell divisions and even be heritable. A major area of research in modern genetics is trying to understand how these modifications affect gene function, particularly the level of gene expression. Therefore, we often consider it an aspect of gene regulation but as we discover more and more about the complexity and far-reaching consequences of epigenetics, it probably deserves to become a separate section.

The pages within our epigenetics section will cover the details about the types of chemical modifications and how they play a role in regulating gene expression. Before starting on these it might be useful to think of an analogy. (As with any analogy you shouldn’t take every part of it too literally!) If you think of the nucleotide sequence of a chromosome as the text of a book (so that the letters in the book correspond to nucleotides) then when we discuss mutations and alleles we are discussing changes in the DNA sequence or variant forms of a gene. Therefore, in our analogy the text of the book would change, or the texts of two different books would be slightly different. Much of Genetics in the 20th century was interested in studying how these differences affected phenotype (along with how genes functioned of course).

Epigenetics studies a different aspect of genetics. The chemical modifications mentioned in the definition above do not change the text of the book. Instead they add markers to the book that change how the text is read by the cell. As you study from a hard copy book you might highlight certain sections or add tabs to pages to make them easier to find. You may also cross out sections you don’t need to study. These changes do not affect what is written in the book but they can be quite important. They help you to utilize the text more efficiently.

Epigenetic changes are like these changes. The DNA sequence remains the same but the chromatin (the DNA plus associated structural proteins) is (in a way) marked up by the cell. These markings involve chromatin modification either to the DNA itself (perhaps analogous to highlighting text) or to proteins like histone (perhaps analogous to adding tabs to pages). These modifications change how the cell uses the DNA - primarily by changing how often it will express a gene near the site of the modifications. Some marks will enhance the rate of expression, so some marks are analogous to any marking you make to tell you that it is an important part of there text to study. Other marks shut down expression of nearby genes, so they are analogous to you marking out a section of text that you know you don’t need to study.

A good way, then, to summarize it is to think of epigenetic changes as changes that alter gene expression - how the genes are used but not the sequences of the genes. One reason that this has been getting a lot of attention recently is that the changes can persist for a long time. Epigenetic changes during early development can persist through a person’s life and even be passed on to future generations. This means that environmental influences, such as diet, early in life can have long-term, perhaps permanent, influences on a person.

To understand this process overall it is probably best to break it into two separate components, the modifications that are made and then how these modifications affect gene expression:

Chromatin Modification: There are two major types of modification; the first is histone modification (modification of a histone protein within the nucleosome core) and the second is modification of DNA, primarily methylation of Cytosines at CG dinucleotides.

Chromatin (or Nucleosome) Remodeling: Chromatin modifications lead to changes in the structure of the chromatin, which is called chromatin remodeling. The specific structural change depends on what modifications have occurred but in general we find that the remodeling can either open up (loosen) the chromatin packaging, thus facilitating gene expression, or it can condense the chromatin, which leads to a reduction in gene expression, often even complete gene silencing. The basic ideas are covered in the page on Eukaryotic Chromosomes, without the context of modifications.

There are many proteins involved in epigenetic changes and these proteins are classified into three general types:

• Writers: A writer is a protein that adds a modification.


• Erasers: An eraser is a protein that removes a modification.


• Readers: A reader is a protein that binds to a modification. Once bound it either directly or indirectly causes a change in gene expression. Some readers are also a writer or an eraser: when these bind the change they make is more chromatin modification. Other readers induce chromatin remodeling.

Summary: The basic process is that writers and erasers add and remove chromatin modifications in response to certain signals, many of which are not well understood. When a writer adds a modification, readers can then bind to the modifications; the general terminology is that the readers are ’recruited’. Ultimately, the recruitment of readers results in changes in how the chromatin is structured and the structure has an effect on gene expression levels. This can also be considered in reverse: when an eraser removes a modification the reader no longer binds and whatever effect it was causing is lost. The links within Epigenetic Mechanisms will cover details about the modifications, the proteins involved, and some basics of chromatin remodeling.