Epigenetics 101 – Nature, Nurture, and Nutrition

By Lara Park, MS

Think that the DNA code you’re dealt is the be-all-end-all for disease risk? A body of research is now demonstrating that nutrition can change how your genome functions by altering the folding of your DNA. This regulation of packaging is called epigenetics, and it is shedding new light on the nature versus nurture debate.

Why do individuals have different susceptibilities to disease? In 2003 when the Human Genome Project was coming to a close, there was a belief that the field of medical research would become increasingly obsolete because all diseases were thought to originate from differences in DNA sequence. In the years since, it has become evident that how the DNA responds to the environment plays a critical role in determining disease susceptibility. DNA contains the blueprint to make every kind of protein in the body, but a library of blueprints is not very useful without any instructions about what to build and when to build it. Epigenetics are the instructions to the DNA blueprint. The food we eat serves as a daily environmental exposure that can modify which genes are turned on and off through changes in epigenetic patterns.

Photo Source

Every single cell in our body contains over six feet of string-like DNA, which needs to fit inside the 15-micron nucleus. In order to fit, the DNA is wrapped around bead-like proteins called histones, and then these beads-on-a-string are tightly wound up into chromosomes. In order to turn on a gene, the packaging around this gene needs to be loosened by adding biochemical compounds to the histone beads. When the gene is turned off, the gene is tightly packaged by adding compounds such as methyl groups directly to the DNA. Epigenetics is the pattern of these compounds on the DNA and its supporting histone structure. This gives DNA two separate identities; one being the DNA code and the other the epigenetic packaging.

Individuals display highly variable epigenetic patterns. The cause of this variability appears to arise from our environment, blurring the distinctions between nature and nurture. Environmental exposures such as diet, pollution, and even stress, can alter epigenetic patterns changing which genes are turned on and off to ultimately affect physiological function. Studies in monozygotic twins with identical DNA demonstrated that older twins, who would have experienced more variable environments, had significantly different DNA methylation patterns compared to young twins. These differences were even more substantial for twins reared apart with a less shared environment. The researchers used a technique to make the DNA methylation patterns on one twin fluoresce green and the other twin fluoresce red, with regions where patterns were identical appeared yellow. While this study was correlational in nature, these visually striking results highlight potential roles of the environment on identical DNA.

DNA methylation in 3 year old twins (left) and 50 year old twins (right).

Nutrition is a daily environmental exposure that contributes to these variations in epigenetic patterns. Studies in cell culture, animal models and humans have identified many dietary compounds that affect epigenetics patterns. Diets deficient in the B vitamins such as folate and vitamin B12 are associated with increased cancer risk across many tissues because these nutrients are the source for methyl groups required for epigenetic DNA methylation. Changes in DNA methylation are one of the earliest steps in cancer development. Curcumin, a polyphenol in the Indian spice turmeric, interacts with the enzymes that place epigenetic marks on histone bead proteins to turn off inflammatory genes in blood cells when blood glucose is high, as seen with diabetes. This suggests that increased curcumin consumption may reduce some of the complications of diabetes, though this hasn’t been thoroughly investigated in humans yet. Similarly, sulfurophane compounds in cruciferous vegetables such as broccoli and brussel sprouts modify histone epigenetic marks at genes that prevent cancer development in colon and prostate cancer cells. While many of these studies suggest potential preventative (and delicious!) therapeutic approaches to disease, research supporting these mechanisms has been challenging in humans. This is in part due to variability in human metabolism, difficulty in quantifying dietary exposure and logistical challenges in acquiring informative tissue samples at appropriate timing in disease progression from free-living humans.

Environmentally induced epigenetic changes can persist even after the exposure is gone. Epigenetics has become particularly relevant to elucidate the mechanisms underlying the fetal origins of disease theory, famously known as the Barker hypothesis. In 1989, David Barker made the observation that low birth weight infants had an increased risk of coronary artery disease, stroke and type II diabetes later in life. A role for epigenetics in the Barker hypothesis was identifiedin the DNA methylation analysis of blood samples from adults who were in utero during the Dutch Hunger Winter when Germany imposed a food embargo on the Netherlands during World War II. Adults with pre-natal famine exposure had impaired glucose tolerance with reduced DNA methylation at the insulin-like growth-factor II (IGF2) gene compared to their non-famine exposed siblings. IGF2 plays a role in insulin signaling during fetal development, making it biologically plausible that it contributed to diabetes susceptibility later in life. These transgenerational epigenetics are hypothesized to contribute to the predictive adaptive response in which the fetus uses the in utero environment to prepare for the post-natal environment. Similar to the Dutch Hunger Winter, many studies have demonstrated that maternal malnutrition leads to fetal epigenetic programming that enhances storage of energy as fat, which turns out to be maladaptive in the post-natal life of food abundance.

The social environment has also been identified as an input in early-life epigenetic programming. Animal models with reduced maternal behaviors, quantified as time spent licking and grooming (LG) of offspring, demonstrated that low-LG offspring had differential DNA methylation of the glucocorticoid receptor in the brain. This turned on the glucocorticoid receptor gene, which functions to regulate the stress response. In humans, suicide victims who were exposed to early life adversity also demonstrated methylation differences at the glucocorticoid receptor gene in the brain compared to non-suicide victims without early life adversity. Taken together, this suggests that early social environments can lead to persistent epigenetic changes that may play a role in behavior.

So to answer our initial question, epigenetics encompasses biological, sociological and environmental inputs into our DNA to contribute to variability in disease risk. What do we do with this information? Well, we can spread the word by dancing about it, as seen in this Dance your PhD entry! On a more serious note, we can be cognizant that our lifestyle choices can impact our DNA such that our health outcomes are truly a balance between nature and nurture. Epigenetic patterns can be viewed as our life history on our DNA and serve as an empowering message to strive for a healthy lifestyle.

*Photo 2 source:  Fraga et al. Epigenetic differences arise during the lifetime of monozygotic twins. PNAS 2005; 102(30):10604-10609

Lara Park is a PhD student in the Biochemical and Molecular Nutrition program working in nutritional epigenetics with Dr. Sang-Woon Choi. Her thesis work is investigating how genome wide epigenetic patterns change with aging and whether a Western-style diet or calorie restricted diet can modify these patterns. Outside of the science world, Lara dances with Urbanity Dance, a Boston-based contemporary dance company.

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s