Written & Researched by Lily Curtis
In comparison to genetic changes which alter the DNA sequence, the study of epigenetics observes how the body reads DNA through gene expression. A predominant value of epigenetics is freeing the study of genetics from the predeterminations of DNA. Rather than changing the DNA sequence, epigenetic markers can act as tags on genes, turning them on or off, for better or for worse. The majority of epigenetic manipulations happen naturally through environmental influences, providing humans with the opportunity to change how their DNA is read by having healthier lifestyle habits, and possibly avoid dangerous, heritable traits. Owing to comparing the genotypes and phenotypes of an organism, epigenetics allows nurture, an organism’s surroundings, an extra hand above nature, an organism’s constant DNA. Studies on epigenetic manipulation of vulnerability towards pathogens, specifically DNA methylation and histone modification, has provided new methods of diagnosing malignants, acting as biomarkers, determining treatments for patients, and predicting lifespan.
Epigenetics are the key components to cell development. Although all cells have the same sequence of DNA, they look and act differently depending on their specified purpose. Much of cell differentiation happens in the embryo, when an organism is composed of only a few embryonic stem cells. Cells receive signals from other cells, causing certain genes to turn off and specific cells are formed. A peer reviewed source shows the distinctions between a muscle cell and neuron cell (1). Although both contain the same DNA, the nerve cell has the capability of transferring information to the brain while the muscle cell is structured to aid the body in its ability to move. Epigenetics allows the muscle cell to turn “on” genes to make proteins important for its job and turn “off” genes important for a nerve cell’s job.
One human body holds over fifty trillion cells, each cell containing six linear feet of DNA. One of the most common epigenetic manipulations is histone modification. In order for DNA to be able to fit within the nucleus, it is wrapped around clusters of proteins called histones. As defined by the National Human Genome Research Institute, the combination of a histone and DNA is called chromatin, in which each cell has on average 30 million (2). Epigenetics modulate the structure of chromatin, thereby affecting the transcription of genes in the genome. If the genes are wrapped too tightly around the histone, they are unable to be read. Epigenetic marks can hook to chromatin, giving it instructions on whether to compact or decompress (3).
One form of histone modification is histone acetylation, where acetyl functional groups are transferred from one molecule to another. Acetylation removes positive charges on histones and decreases the interaction of histones with the negatively charged phosphate groups of DNA. A study done by Chandra, Aneesh et al on histone acetylation has proved essential in understanding the cause of immune system vulnerability to tuberculosis, therefore, introducing new and more effective forms of treatment (4). Tuberculosis is responsible for over 1.4 million deaths a year across the world. It’s success relies heavily on its ability to invade and thrive within the macrophages of a host. Upon invasion, mycobacterium tuberculosis (MTB), the causative infectious agent, causes changes to histones in immune cells by turning ‘off’ the Il-12B gene. Turning off this gene prevents acidification and maturation of phagosomes, so that the germ can avoid professional phagocytes. Without the threat of phagocytes, the pathogen is given sufficient time for the bacterium to establish persistent infection and thwart pro-inflammatory responses. The journal suggests, “ … change the environment in which the pathogen exists to make it less favorable for the pathogen to live and grow.” Instead of targeting pathogens directly, like traditional antibiotics do, the study proves a promising strategy of host directed therapies that inhibit MTB from being able to bide time to invade.
Stay tuned for part 2 on DNA methylation next month!
References
(1) Kiefer, Julie C. “Epigenetics in development.” Developmental dynamics : an official publication of the American Association of Anatomists vol. 236,4 (2007): 1144-56
(2) “Chromatin.” National Human Genome Research Institute. September 3, 2020.
(3) “What is Epigenetics?” CDC. August 3, 2020.
(4) Chandran, Aneesh et al. “Mycobacterium tuberculosis Infection Induces HDAC1-Mediated Suppression of IL-12B Gene Expression in Macrophages.” Frontiers in cellular and infection microbiology vol. 5 90. 2 Dec. 2015.