Did you know that you have the power to change your own genes? “Epigenetics”; the meaning of this word is as simple as it sounds, though how it works exactly is still an answer the scientific world is behind. Coming from a history of scientists and researchers trying to redefine the term, today Epigenetics is defined as
‘‘the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence.’’ We cannot move ahead into this topic without mentioning the person responsible for introducing the term. Conrad Waddington introduced the term epigenetics in the early 1940s. He defined epigenetics as ‘‘the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being.’’ This definition has been narrowed down in today’s time and age, but still remains in question. If I were to explain this in simpler terms, I would simply describe it as a functional or structural change seen in our body without the DNA molecule having to be remodeled.
The concept of Epigenome:
The DNA in our body has all the genetic information on building all the parts of our body, but that is only half the story. The DNA molecule is then wrapped around with proteins called histones which are further covered with chemical tags. This entire structure makes the epigenome. The epigenome is responsible for the physical structure of the genome, it modulates this by tightly wrapping inactive genes making them unreadable and lightly wrapping the active ones. It is the DNA sequence that remains the same for a lifetime, but the epigenome is affected by external conditions like dietary habits, stress, exercise, etc. adjusting genes accordingly. The chemical tags are known to be sensitive to such factors.
Lick your rats:
An interesting concept of “Lick your rats” came up while reading about this topic. It was in one Dr. Moshe Szyf’s lectures, where he talks about the nurturing of rats. In this concept, some mother rats spend a lot of time licking and nurturing rat babies making them very calm whereas others who are not taken care of very well, end up being anxious individuals. When we observe this, we can easily understand how epigenetics can be flexible to a point that extends beyond the relatively fixed DNA code. The licking and grooming (LG) and arched-back nursing (ABN) by rat mothers alters the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. This also results in changes seen in the DNA methylation of these high LG and ABN rats compared to the low LG and ABN rats. It was also observed that cross fostering made some reversible changes that persisted through adulthood. The epigenetic code allows certain types of information to be passed to offspring without having to go through the slow processes of random mutation and natural selection. At the same time, the epigenetic code is sensitive to changing environmental conditions such as availability of food or threat from predators. All that being said, we also need to understand how the whole change is reversible for each of the rat babies. Inducing the brain with drugs removing methyl groups, an anxious rat baby can be made calm.
Cancer in epigenetics:
Brushing up about the clinical significance of cancer in epigenetic studies, cancer is when a cell grows out of control. It can begin when there is mutation of a DNA sequence. But epigenomes also play a crucial role in the development of cancer. In various studies it is observed that the disruption of stem/progenitor cells along with tumor progenitor cells have led to development of cancer. The cancer epigenome is characterized by global changes in DNA methylation and histone modification patterns as well as altered expression profiles of chromatin-modifying enzymes.
Clinical Significance:
Epigenetics has its role in transgenerational inheritance, its clinical significance also comes into focus when we talk about children conceived using assistive reproductive technology, prevalence of cancer, coronary heart disease, stroke and diabetes. Many research documents on the same can be found suggesting that in-utero malnutrition and low birth weight lead to more risk of heart disease, diabetes and stroke.
Psst—–Have you heard the new gossip in town?
Metabolic diseases are showing love interest in the lover boy Epigenetics?
In recent studies, it is proven that metabolic diseases are associated with epigenetics. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Multiple epigenetic modifications are significantly correlated with metabolic disease-related gene function and expression and often occur early in diseases, thus exhibiting promising potential as clinical biomarkers for patients with metabolic diseases. According to a study, The methylation level of PHOSPHO1 is negatively correlated with the risk of T2D(type 2 DM), while the methylation level of ABCG1 is associated with an elevated risk of T2D. Johnson et al identified seven CpG sites, which are could act as promising biomarkers for liver fibrosis. But as promising as this love story may sound, there are great differences between individuals and small alterations could accumulate to make a big difference due to the heterogeneity of metabolic diseases, making it one of the challenges faced today. There is a great need to develop more epigenetic drugs and related technologies for metabolic diseases, endeavors that require broader cooperation. This is an area with great potential, and many problems still need to be explored.
When we talk about Epigenetics and its relation to the brain, it does become quite the casanova. In Parkinson’s disease, DNA methylation changes are associated with both familial and sporadic forms, highlighting the broad impact of epigenetic factors. Another study suggests the association of Alzheimer’s disease progression due to contribution of specific epigenetic changes like DNA methylation and histone modifications. Epigenetics is crucial in understanding and treating psychiatric disorders, revealing the interplay between genetics, epigenetics, and environmental factors. Epigenetic changes in genes related to neurotransmitter systems and stress response have been found in depression, offering new treatment approaches. Epigenetic marker alterations have been identified in bipolar disorder, giving us immense understanding of the complex disorder.
As this field emerges we can expect some really promising outcomes, taking us closer to curing a variety of illnesses in the future.
