DNA marks in adults tracked back to changes in earliest days of life

July 11, 2018, London School of Hygiene & Tropical Medicine
A depiction of the double helical structure of DNA. Its four coding units (A, T, C, G) are color-coded in pink, orange, purple and yellow. Credit: NHGRI

Scientists have gained a glimpse of how marks on our genes that could be linked to adverse health outcomes in later life behave differently in the first few days after conception, according to new research published in Science Advances.

Some of these marks have been associated with the environment experienced by the developing embryo, including differences in maternal nutrition. The research team, led by scientists at the Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine (LSHTM), say the study is an important step in understanding a mechanism by which the embryo responds to its early environment, with the potential to influence health in later life.

The genes we inherit from our parents are overlaid by a complex set of instructions that govern how they are expressed. These so-called 'epigenetic' marks come in a range of different forms and control many vital processes within . For example, every cell in the body contains an identical set of inherited genes, but epigenetic marks ensure that different combinations of genes are switched on or off to make the various cell types, such as muscle, bone and nerves.

The researchers studied specialised regions of the genome (known as metastable epialleles or MEs) where the epigenetic (methylation) marks are laid down in the first few days following conception. As in previous studies, MEs were identified by analysing cells from adults and children, but until now scientists have had no way of understanding how these marks behave in the first few days after conception.

To examine this the researchers used publicly available data from Chinese human embryos, conceived through In vitro fertilisation (IVF). This included measures of DNA methylation from multiple stages during early embryonic development, including sperm and egg cells, and time points where the embryo consists of just a few cells.

The team tracked the patterns of erasure and re-establishment of the DNA marks in the first week of life. They then compared this with in fully-differentiated embryonic liver cells from between six and 10 weeks gestation.

They found that MEs show atypical patterns of establishment in these embryos, compared to other regions on the genome.

In contrast to the great majority of methylation sites across the genome which are either fully methylated or unmethylated in all cells, ME methylation is much more variable in embryonic liver and other differentiated tissues. This suggests that the establishment of methylation at MEs may be sensitive to external environmental factors.

The researchers say that these regions could have evolved to sense the nutritional environment, record the information on DNA and adapt the baby to be best suited to its circumstances.

In addition, the researchers were able to characterise other factors related to the position of MEs within the genome which may provide further clues to explain their unusual behaviour.

Dr. Matt Silver, senior author at MRC Unit The Gambia at LSHTM, said: "Previously our work has indicated that epigenetic marks in these regions are associated with differences in around the time of conception, and several MEs have been linked to important health outcomes in later life, although further work is needed to confirm this.

"Here, for the first time, we've been able to gain insight into how these marks are being established in the early embryo. Our discovery that they behave in a distinctive fashion in the earliest days of life is an important step in understanding how our very early environment might influence our development and future health."

Previous research using an 'experiment of nature' in The Gambia, where dietary patterns vary significantly between rainy and dry seasons, has suggested that methylation patterns at MEs are affected by a mother's (and possibly a father's) nutritional status.

There is also evidence that methylation states at certain MEs are associated with an increased risk of cancers and obesity.

Professor Andrew Prentice, co-author at MRC Unit The Gambia at LSHTM, said: "We cannot alter the genes that we inherit from our parents, but our work suggests we might be able to alter epigenetic patterns that govern how these genes function. The fact that certain are sensitive to nutrient inputs at the time of conception focusses attention on how crucial it is—for both parents—to eat a healthy and balanced diet before starting a pregnancy.

"These findings also offer the exciting possibility of developing interventions before conception, which might reduce the risk of diseases in the offspring and even in future generations."

More work is now needed to establish which components of a mother's and father's diet and other environmental factors are able to influence DNA methylation patterns in the early embryo, and to better understand how these might link to adverse health outcomes in later life. This will involve further work in cells and further studies in diverse human populations linking diet, epigenetics and health.

The authors acknowledge limitations to their study, including the small number of embryos studied, and the difficulty of gaining a definitive understanding of the extent to which genetic variation can influence DNA methylation at MEs. Furthermore, methylation changes are obtained by analysing methylation in different , each measured at different time points. This is necessary since it is not currently possible to measure methylation changes in the same cells across time.

Explore further: Mom's in control—even before you're born

More information: Noah J. Kessler, Robert A. Waterland, Andrew M. Prentice and Matt J. Silver. Establishment of environmentally-sensitive DNA methylation states in the very early human embryo. Science Advances. , DOI: 10.1126/sciadv.aat2624 , http://advances.sciencemag.org/content/4/7/eaat2624

Related Stories

Mom's in control—even before you're born

January 25, 2016
Researchers have uncovered previously unappreciated means by which epigenetic information contained in the egg influences the development of the placenta during pregnancy. The research, which was performed in mice, indicates ...

Understanding how DNA is selectively tagged with 'do not use' marks

May 7, 2018
Not all of your genome needs to be active at any given time. Some regions are prone to hopping around the genome in problematic ways if left unchecked; others code for genes that need to be turned off in certain cells or ...

Mother's environment before conception may affect her child's life long risk of disease

June 10, 2015
Scientists have shown for the first time that a mother's environment around the time of conception could permanently change the function of a gene influencing immunity and cancer risk in her child.

Early epigenetic switches associated with childhood bone health

May 10, 2017
The health of children's bones could be determined before they are born, a new University of Southampton study has shown.

Modulation of Fgf21 gene in early-life ameliorates adulthood diet-induced obesity

March 12, 2018
The importance of good nutrition in the early development of children has been recognized for many decades. Nutritional experiences in early life can have profound and long-lasting effects on body weight in later life. For ...

Mother's diet affects the 'silencing' of her child's genes

April 29, 2014
A mother's diet before conception can permanently affect how her child's genes function, according to a study published in Nature Communications.

Recommended for you

Progress in genetic testing of embryos stokes fears of designer babies

November 16, 2018
Recent announcements by two biotechnology companies have stoked fears that designer babies could soon be an option for those who can afford to pick and choose which features they want for their offspring. The companies, MyOme ...

Gene editing possible for kidney disease

November 16, 2018
For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

DICE: Immune cell atlas goes live

November 15, 2018
Compare any two people's DNA and you will find millions of points where their genetic codes differ. Now, scientists at La Jolla Institute for Immunology (LJI) are sharing a trove of data that will be critical for deciphering ...

Ashkenazi Jewish founder mutation identified for Leigh Syndrome

November 15, 2018
Over 30 years ago, Marsha and Allen Barnett lost their sons to a puzzling childhood disease that relentlessly attacked their nervous systems and sapped their energy. After five-year-old Chuckie died suddenly in 1981, doctors ...

Drug candidate may recover vocal abilities lost to ADNP syndrome

November 15, 2018
Activity-dependent neuroprotective protein syndrome (ADNP syndrome) is a rare genetic condition that causes developmental delays, intellectual disability and autism spectrum disorder symptoms in thousands of children worldwide. ...

The puzzle of a mutated gene lurking behind many Parkinson's cases

November 15, 2018
Genetic mutations affecting a single gene play an outsized role in Parkinson's disease. The mutations are generally responsible for the mass die-off of a set of dopamine-secreting, or dopaminergic, nerve cells in the brain ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.