Epigenetics: Driver of Change

Authored by: Nisha Sodhi

DNA makes RNA which makes protein. Many may have heard this sequence in their introductory biology class. For those unfamiliar, this phrase provides insight into how genetic information is translated into proteins critical for bodily functions. However, this simple sequence of events fails to provide insight into how the same DNA sequence can give rise to different proteins, thus leading to varying expressions of traits at the cellular and physiological levels. These changes are studied under the field of epigenetics, or the “study of changes in gene function that are mitotically and/or meiotically heritable and [do] not entail a change in DNA” [1]. In essence, epigenetics seeks to understand the different mechanisms through which gene expression is manipulated. This article explores the mechanisms that influence gene expression and how sometimes, these changes can have negative health outcomes, specifically related to brain disorders. The importance of understanding epigenetic markers in the early detection of these diseases will also be explored. 

One major mechanism of epigenetic regulation is DNA methylation, which can suppress or activate certain genes, causing variations in cellular processes. DNA methylation results from the transfer of a methyl group (-CH3) from one point on the DNA to another. This transfer either favors or disfavors the transcription of DNA to RNA, which influences protein synthesis. These methylation markers depend upon environmental factors and stresses imposed during embryonic stages of development [2]. While DNA methylation is a common process and critical in molding the genome, unregulated suppression and activation of genes can have negative health outcomes. For example, a lack of DNA methylation in repeated genomic sequences can lead to cancer, while too much methylation can cause several autoimmune and autoinflammatory diseases [3]. Therefore, proper regulation of gene expression is critical for maintaining homeostasis. 

Understanding how the environment influences gene expression can provide further insight for determining who may be at a higher risk for abnormal methylation patterns and developing certain diseases and disorders. An example of the environment influencing gene regulation can be seen through a study conducted by Dr. Shuk-Mei Ho from the University of Arkansas, which analyzed the impact of inhalation of surrounding tobacco smoke on gene expression. The results revealed that tobacco smoke led to DNA hypomethylation of a specific gene. This leads to the increased expression of oncogenes, which contributes to the development of cancer cells [4]. An individual who lives in a neighborhood with a higher rate of smokers and exposure to tobacco smoke may, therefore, have a higher risk of developing cancer later on in their lifetime. Thus, understanding the gene expression mechanisms and their relationship with environmental stressors can help researchers and physicians better understand and detect regions of DNA that may become problematic. 

The knowledge gained from DNA methylation research can be used for disease screening and prevention. Identifying DNA methylation sites can be used as a biomarker to help detect susceptibility for neurodegenerative diseases such as Alzheimer's disease and schizophrenia earlier in life. Furthermore, the detection of abnormal DNA methylation encourages researchers to develop drugs that can counteract the onset of these disorders by altering DNA methylation patterns [5].

Health is a multifaceted concept, from the genomic level all the way to the environmental and social level. However, all of these layers are interdependent, and disruption in one can lead to the onset of negative health outcomes. Therefore, it is critical to understand how gene expression works and what affects these traits so that the prognosis of diseases and disorders can be detected early on to promote longevity and well-being. 

References:

1. Dupont, C., Armant, D., & Brenner, C. (2009). Epigenetics: Definition, mechanisms and

   clinical perspective. Seminars in Reproductive Medicine, 27(05), 351–357. https://doi.org/10.1055/s-0029-1237423 

2. Dhar, G. A., Saha, S., Mitra, P., & Nag Chaudhuri, R. (2021). DNA methylation and

   regulation of gene expression: Guardian of Our Health. The Nucleus, 64(3), 259–270. https://doi.org/10.1007/s13237-021-00367-y

3. Ehrlich, M. (2019). DNA hypermethylation in disease: Mechanisms and clinical

   relevance. Epigenetics, 14(12), 1141–1163. https://doi.org/10.1080/15592294.2019.1638701 

4. Ho, S.-M., Johnson, A., Tarapore, P., Janakiram, V., Zhang, X., & Leung, Y.-K. (2012).

   Environmental epigenetics and its implication on disease risk and health outcomes. ILAR Journal, 53(3–4), 289–305. https://doi.org/10.1093/ilar.53.3-4.289 

5. Levenson, V. V. (2010). DNA methylation as a universal biomarker. Expert Review of

   Molecular Diagnostics, 10(4), 481–488. https://doi.org/10.1586/erm.10.17