Who you are is not just down to your DNA; your environment plays a big role, too. Lifestyle factors such as stress and diet can alter the way your genes are tagged with on and off switches, which modify the way your genes are expressed. While this much was known, how these changes seem to be passed on to future generations has puzzled scientists. Now, a new study has finally provided some insight into what’s going on.
Although early cells destined to become eggs and sperm are wiped of these changes early on in embryo development, scientists have revealed that some stretches of DNA resist this so-called reprogramming, allowing the modifications to persist and thus become heritable. Importantly, the researchers discovered that some of the resistant genes are associated with certain diseases, including obesity and schizophrenia. These intriguing findings have been published in the journal Cell.
While DNA contains the codes necessary to build an organism, not all of our genes need to be active at the same time or in the same place throughout the body. This is where epigenetics come in; these modifications to DNA can alter which genes are turned on or off without changing the actual DNA sequence itself. For example, a chemical tag called a methyl group can be added or removed that can inactivate genes by making the DNA inaccessible to the machinery that comes along to read it.
This process of DNA methylation continues throughout our lives, but it can also occur in response to factors in the environment. For example, stress such as famine can alter methylation patterns, and an increase in the risk of schizophrenia has even been found in girls born to mothers who experienced prolonged periods of famine during pregnancy. But it doesn’t end there; mice subjected to stress in the lab have been shown to produce two generations of depressed offspring, even though their upbringing was not stressful.
These observations are perplexing because epigenetic data was thought to be erased in the cells that give rise to sperm and egg cells, called germ cells, to prevent any abnormal methylation from accumulating that could harm offspring. In an attempt to solve this apparent mystery, scientists from the University of Cambridge began examining the processes at play in developing mice embryos. In particular, they were interested in the embryo’s germ cells since these are what will eventually give rise to the animal’s offspring.
They found that the process of germ cell reprogramming takes place over a period of roughly seven weeks, kicking off around two weeks into embryo development. This clearance phase involves the initiation of an inhibitory network that prevents the action of enzymes that facilitate epigenetic changes or their maintenance. However, they found that around 5% of the genome resisted reprogramming. This means that any methylation that has occurred in these regions is not removed and can thus persist, potentially impacting future generations.
Upon closer inspection, the researchers revealed that some of these resistant regions are associated with certain conditions, including diabetes, obesity and schizophrenia. These reprogramming “escapees” could therefore help explain why environmental factors can not only impact an individual’s health, but the health of their future generations.