Editor’s Note: Following an “epigenetics” discussion in class, one of our participants, who is also a molecular biologist, kindly volunteered to write this article. This is a very edited-down version of her article (my apologies to her). To request a copy of her original version, which is longer and quite scholarly, please email email@example.com.
Replied to by Dr. S. Ansari
“Epigenetics” is an emerging field of science that involves the study of changes in the “reading” of gene activity that determines which genes are expressed. It has been dubbed “epigenetics,” from the prefix epi (Greek for over, outer, above). Diverse biological characteristics can be affected by epigenetic mechanisms, for example, the shape and colour of flowers, and eye colour in fruit flies. Epigenetic changes can be caused by many different environmental and behavioural factors.
These epigenetic changes can switch genes on or off, and are involved in many normal cellular processes. Consider the fact that our bodies contain many different types of cells: neurons, liver cells, pancreatic cells, inflammatory cells, etc. How is this possible when they all contain the same DNA (the content of genes)? In short, cells, tissues, and organs differ because they have certain sets of genes that are “turned on” or expressed, as well as other sets that are “turned off” or inhibited. Epigenetic “silencing” is one way to turn genes off and might also explain, in part, why identical twins are not absolutely identical and can exhibit diseases differently. In addition, epigenetics is important for understanding X (sex)-chromosome inactivation in female mammals (they have twice the number of X-chromosome gene products as males ). Thus, the significance of turning genes off via epigenetic changes is readily apparent. Also, there are different ways epigenetics can work in cells to silence genes, which involve chemical changes at the beginning part of the gene.
Epigenetics and Cancer: The first human disease to be linked to epigenetics was cancer in 1983. Researchers found that diseased tissue from patients with colorectal cancer had evidence of epigenetic disruption when compared with normal tissue from the same patients . There appeared to be silencing of a tumour suppressor gene that keeps the growth of abnormal cells in check, leading to uncontrolled cellular growth. Another example is an epigenetic change that “turns off” genes which help repair damaged DNA. This leads to an increase in DNA damage, which in turn increases the risk of cancer.
Epigenetics and Inheritance: Geneticists were particularly surprised to find that epigenetic change could be passed down from parent to child, one generation to the next. Researchers showed that when female mice were fed a diet rich in methyl groups, the fur pigment of subsequent offspring was permanently altered . Without any change to DNA at all, the expression/inhibition of genes was inherited from their ancestors much like a gene mutation.
Behavioural Epigenetics: It is known that diet and chemicals can cause epigenetic changes. But can certain experiences such as drug abuse, child neglect, or other severe stresses also trigger epigenetic changes inside the neurons of a person’s brain? This research formed the basis of a new field: behavioural epigenetics, which has suggested profound new treatments to heal the brain. Scientists have discovered that traumatic experiences in our past, or in our recent ancestors’ past, leave molecular “scars” adhering to our DNA. Examples include adults of every ethnicity who grew up with alcoholic or abusive parents; young immigrants from Africa whose parents survived massacres; those with Chinese grandparents that lived through the ravages of the Cultural Revolution; and, Jews whose great-grandparents were chased from their Russian shelters. They all carry with them more than just memories.
In addition, scientists have found that inattentive mothering in rodents causes changes in the genes for estrogen receptors in the brain. When those babies grow up, the resulting decrease in estrogen receptors makes them less attentive to their own babies .
Epigenetics and Mental Retardation: “Fragile X syndrome” is the most frequently inherited mental disability, particularly in males, leading to severe intellectual disabilities, delayed verbal development, and “autistic-like” behaviour. Studies show that individuals with this syndrome have a more “turned off” gene than normal, stopping the gene from producing an important protein. Other such mental disorders with altered epigenetic mechanisms have also been discovered .
Epigenetic Therapy: Because so many diseases, such as cancer, involve epigenetic changes, it seems reasonable to try to counteract cancerous growths with epigenetic treatments. However, to be successful, epigenetic treatments must be selective or specific to the diseased cells. Otherwise, changing gene expression in normal cells could make them cancerous, causing the very disorders they are trying to counteract. Despite these possible drawbacks, epigenetic therapy is increasingly promising as researchers are finding ways to specifically target abnormal cells with minimal damage to normal cells .
- Egger G, Liang G, Aparicio A, Jones PA. “Epigenetics in human disease and prospects for epigenetic therapy.”Nature. 2004; 429(6990): 457-63.
- Feinberg AP, Vogelstein B. “Hypomethylation distinguishes genes of some human cancers from their normal counterparts.” Nature. 1983; 301(5895): 89-92.
- Dolinoy DC, Huang D, Jirtle RL. “Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development.” Proc Natl Acad Sci U S A. 2007; 104(32): 13056-61.
- Hurley, D. “Grandma’s Experiences Leave a Mark on Your Genes:” Discover May 2013
- Weaver ICG, Cervoni N, Champagne FA, D’Alessio AC, Sharma, S, Seckl JR, Dymov S, Szyf M, Meaney MJ. “Epigenetic programming by maternal behavior.” (2004) Nat Neurosci. 2004; 7(8): 847- 54.
- Penagarikano O, Mulle JG, Warren ST. “The pathophysiology of fragile x syndrome.” Ann Rev Genomics Hum Genet. 2007; 8: 109-29.