Epigenetics: Fundamentals

Epigenetics is the study of heritable changes in gene expression (active versus inactive genes) that do not involve changes to the underlying DNA sequence — a change in phenotype without a change in genotype — which in turn affects how cells read the genes.

Epigenetic change is a regular and natural occurrence but can also be influenced by several factors including age, the environment/lifestyle, and disease state. Epigenetic modifications can manifest as commonly as the manner in which cells terminally differentiate to end up as skin cells, liver cells, brain cells, etc. Or, epigenetic change can have more damaging effects that can result in diseases like cancer. At least three systems including DNA methylation, histone modification and non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic change.1 New and ongoing research is continuously uncovering the role of epigenetics in a variety of human disorders and fatal diseases.

The Evolving Landscape of Epigenetic Research: A Brief History

What began as broad research focused on combining genetics and developmental biology by well-respected scientists including Conrad H. Waddington and Ernst Hadorn during the mid-twentieth century has evolved into the field we currently refer to as epigenetics. The term epigenetics, which was coined by Waddington in 1942, was derived from the Greek word “epigenesis” which originally described the influence of genetic processes on development.2 During the 1990s there became a renewed interest in genetic assimilation. This led to elucidation of the molecular basis of Conrad Waddington’s observations in which environmental stress caused genetic assimilation of certain phenotypic characteristics in Drosophila fruit flies. Since then, research efforts have been focused on unraveling the epigenetic mechanisms related to these types of changes.3

Currently, DNA methylation is one of the most broadly studied and well-characterized epigenetic modifications dating back to studies done by Griffith and Mahler in 1969 which suggested that DNA methylation may be important in long term memory function.4 Other major modifications include chromatin remodelinghistone modifications, and non-coding RNA mechanisms. The renewed interest in epigenetics has led to new findings about the relationship between epigenetic changes and a host of disorders including various cancers, mental retardation associated disorders, immune disorders, neuropsychiatric disorders and pediatric disorders.

Epigenetics and the Environment: How Lifestyle Can Influence Epigenetic Change from One Generation to the Next

The field of epigenetics is quickly growing and with it the understanding that both the environment and individual lifestyle can also directly interact with the genome to influence epigenetic change. These changes may be reflected at various stages throughout a person’s life and even in later generations. For example, human epidemiological studies have provided evidence that prenatal and early postnatal environmental factors influence the adult risk of developing various chronic diseases and behavioral disorders.5 Studies have shown that children born during the period of the Dutch famine from 1944-1945 have increased rates of coronary heart disease and obesity after maternal exposure to famine during early pregnancy compared to those not exposed to famine.6 Less DNA methylation of the insulin-like growth factor II (IGF2) gene, a well-characterized epigenetic locus, was found to be associated with this exposure.7 Likewise, adults that were prenatally exposed to famine conditions have also been reported to have significantly higher incidence of schizophrenia.89

Research has also shown that a mother’s exposure to pollution could impact her child’s asthma susceptibility and her intake of vitamin D could change DNA methylation that influences placenta functioning. It doesn’t stop at the mother, however, as further studies support that the father has a hand in his child’s health and epigenetic marks as well. Read: A Child’s Mental Fitness Could Be Epigenetically Influenced by Dad’s Diet.

How Lifestyle Can Affect Individual Epigenetics and Health

Although our epigenetic marks are more stable during adulthood, they are still thought to be dynamic and modifiable by lifestyle choices and environmental influence. It is becoming more apparent that epigenetic effects occur not just in the womb, but over the full course of a human life span, and that epigenetic changes could be reversed. There are numerous examples of epigenetics that show how different lifestyle choices and environmental exposures can alter marks on top of DNA and play a role in determining health outcomes.

The environment is being investigated as a powerful influence on epigenetic tags and disease susceptibility. Pollution has become a significant focus in this research area as scientists are finding that air pollution could alter methyl tags on DNA and increase one’s risk for neurodegenerative disease. Interestingly, B vitamins may protect against harmful epigenetic effects of pollution and may be able to combat the harmful effects that particular matter has on the body.

Diet has also been shown to modify epigenetic tags in significant ways. The field of nutriepigenomics explores how food and epigenetics work together to influence health and wellbeing. For example, a study found that a high fat, low carb diet could open up chromatin and improve mental ability via HDAC inhibitors. Other studies have found that certain compounds within the foods we consume could protect again cancer by adjusting methyl marks on oncogenes or tumor suppressor genes. Ultimately, an epigenetic diet may guide people toward the optimal food regimen as scientific studies reveal the underlying mechanisms and impact that different foods have on the epigenome and health.

Source

Photo: https://wid.wisc.edu

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