In the past it was believed that DNA was something finite and unchangeable, determining everything from your height to your intelligence to your metabolism. Recently, however, epigenetics, the study of the epigenome, has revealed that DNA can be affected by how we live and what we do.
An individual’s DNA maintains its original sequence throughout his or her life, even after epigenetic changes have affected the way the sequence is transcribed and translated. Epigenetic changes occur in many ways, but the two major mechanisms are chromatin remodeling and DNA methylation. These systems modify the function of DNA without changing its sequence [1]. But what are these changes, what causes them, and how do they help us change?
In the nucleus of eukaryotic cells, DNA is found wrapped around proteins for packaging and structure – this protein and DNA complex is called chromatin. The main element of this complex is a protein molecule called histones. Histone tails extend from the histone, allowing for chemical changes that are catalyzed by particular enzymes. DNA binds to the histones in clumps so that each group of histones forms a bead-like structure called a nucleosome. The DNA holds nucleosomes together like beads on a string [2].
Chromatin remodeling is regulated by the presence of chemical modifications to these proteins. For example, the addition of chemical groups to histone tails can promote or inhibit DNA replication and transcription [3]. But while mutations in genetic information are permanent, epigenetic changes can be reversible. For example, adding acetyl groups to histone tails – histone acetylation – loosens the formation of chromatin, allowing the DNA to become more accessible and easier to transcribe. Adding methyl groups – histone methylation – brings DNA close together to inhibit transcription. Since these biochemical groups do not change the actual content of DNA, they are considered to be epigenetic changes [4].
In DNA methylation, a methyl group is added to cytosine (one of the four main bases in DNA), maintaining the condensed structure of DNA and subsequently preventing transcription [5]. Methylation is found across most of the genome in animals, with varying patterns and concentration. For example, female bee workers and the queen bee are genetically very similar, but when methyl-adding enzymes were reduced in bee larvae, all of the larvae hatched as queen bees. Therefore, the lack of methyl groups allowed special genes to be read and eventually led to the development of queen bees [6]. Out of the many epigenetic mechanisms, DNA methylation was the first discovered and the most well-researched [7].
Epigenetic processes vary in effects, from responses aiding development in the body to epigenetic changes due to pernicious conditions.
As the body matures, epigenetic factors involve themselves in the specialization of cells, in addition to helping regulate gene expression. Epigenetic changes allow for the differentiation between identical pluripotent stem cells as they develop. Even though all the cells in one body contain the exact same DNA, epigenetic processes make it possible for stem cells to differentiate – into eye cells, muscle cells or brain cells [8].
Along with responding to stimuli from inside the body, the epigenome can respond to factors from outside the body as well. The two major factors in epigenetic response to external agents are nutrition and environment. Animal studies reveal that mothers with too little methyl in their diet before childbirth can induce parts of the child’s genome to have a methyl deficiency for the rest of their lives [9]. Exposure to cigarette smoke, ionizing radiation, and pesticides can also modify epigenetic mechanisms. In vitro studies show that this exposure can result in hypomethylation, or a loss of methylation. This hypomethylation in DNA in exposed animals can be linked back to genomic instability – an increase in the likelihood of mutation in the genome [10, 11, 12]. Furthermore, genomic instability is a “driving for tumorigenesis,” the formation of cancer [13].
So epigenetic changes are influenced by a multitude of things, both natural – like cell differentiation – and pernicious – like exposure to cigarette smoke and pesticides. But can these changes be passed on?
Typically, the pattern of methyl groups attached to DNA is mostly destroyed and then reformed during the formation of gametes [2]. But some research has found that alterations in the epigenome can be passed down from generation to generation.
Mice placed under stress can pass their epigenetic changes onto their offspring. One study involved scientists exposing a parent generation of mice to the smell of cherry blossoms. Simultaneously, the mice were electrically shocked. The parents consequently associated pain with the smell of cherry blossoms. And when they had offspring, though the progeny had never been exposed to cherry blossom smell, the mice pups responded anxiously and fearfully in the presence of the smell [14]. This case and many others support the claim that epigenetic changes can be inherited from generation to generation.
Advances in the epigenetic field have paved the way for other opportunities for health improvements as well. Epigenetics is a new, albeit burgeoning, study and the elucidation of the mechanisms of epigenetic changes can be useful in many different ways. Researchers are amassing evidence that epigenetics can be involved in mental disorders [15]. And unlike genetic disorders, epigenetic changes are potentially reversible; techniques like exposure therapy are already used to help treat patients with PSTD [16].
Additionally, recent research has shown that aberrations in epigenetic mechanisms can contribute to the proliferation of malignant cells, and subsequently lead to cancer. Data from Johns Hopkins School of Medicine Center for Epigenetics in Baltimore, Maryland suggests that epigenetic changes are seen in all cancers, and the epigenome is modified in most cancer mutations [17]. With that in mind, the burgeoning field of epigenetic therapy involves drugs inhibiting enzymes that modify histones. Epigenetic therapy has been a promising new treatment for cancer [18].
As mentioned before, the differentiation of cells comes mainly from epigenetic factors. Further investigation into this mechanism promises manifold prospects in regards to the production and development of stem cells, another reason as to why studies of the epigenome can play a vital role in future medicines and treatments.
There are many positive reasons as to why the epigenome should be studied carefully – finding a cure for mental illnesses, understanding cancer, and possibly harnessing the power of stem cells. However, there are also many concerns linked to epigenetic treatments. This includes the effects of epigenetic therapy in cancer or mental illness patients unintentionally inherited by the patients’ children, and the potential for dangerous repercussions of artificially creating or inhibiting epigenetic changes.
The science of epigenetic changes and epigenetic inheritance is still in its early stages. There are many challenges being faced in the study of the epigenome; the interdisciplinary nature of the science behind the epigenome makes research difficult. Even when manipulations of epigenetic mechanisms are successful, providing evidence for the fact that an in vitro epigenetic change might have caused a particular phenotype to be present in the organism remains a quixotic notion [19]. Regardless, potentials and possibilities linked to the epigenome have already been discovered, with many more to come.
Sources:
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