A fundamental discovery about what drives healthy embryonic development could rewrite our understanding of what we inherit from our parents and how their life experiences can shape us.
A new study shows that epigenetic information, which sits on top of DNA and is normally reset between generations, is more often passed down from mother to offspring than previously thought.
The study, led by researchers at WEHI (Melbourne, Australia), significantly expands our understanding of which genes have epigenetic information that is passed from mother to child, and which proteins are important to control this unusual process.
Epigenetics is a rapidly developing field of science that examines how our genes are turned on and off so that a single set of genetic instructions creates hundreds of different types of cells in our body.
Epigenetic changes can be affected by environmental variations, such as our diet, but these changes do not change DNA and are not usually passed from parent to offspring.
While a tiny group of “imprinted” genes can carry epigenetic information across generations, very few other genes have so far been shown to be influenced by the mother’s epigenetic state.
A new study shows that the supply of a specific protein in the mother’s egg cell can affect the genes that control the formation of the offspring’s skeleton.
Principal investigator Professor Marnie Blewitt said the team were initially surprised by the findings.
“It took us a while to process because our discovery was unexpected,” said Professor Blewitt, joint head of WEHI’s Epigenetics and Development Unit.
“Knowing that epigenetic information from the mother can have consequences for shaping the body throughout life is very exciting because it suggests that this happens much more often than we ever thought.
“This could open a Pandora’s box as to what other epigenetic information is inherited.”
The research, carried out by WEHI in collaboration with Associate Professor Edwina McGlynn of Monash University and the Australian Institute of Regenerative Medicine, is published in Communications of nature.
The new study focused on the SMCHD1 protein, an epigenetic regulator discovered by Professor Blewitt in 2008, and Hox genes that are important for normal skeletal development.
Hox genes control the identity of each vertebra during embryonic development in mammals, while an epigenetic regulator prevents these genes from being activated too early.
In this study, the researchers found that the amount of SMCHD1 in the mother’s egg affects activity Hox genes and affects the pattern of the embryo. Without maternal SMCHD1 in the egg, offspring were born with altered skeletal structures.
First author and Ph.D. Natalia Benetti said this is clear evidence that epigenetic information was inherited from the mother, rather than just genetic information.
“Although there are more than 20,000 genes in our genome, only this rare subset of about 150 imprinted genes and very few others have been shown to carry epigenetic information from one generation to the next,” Benetti said.
“Knowing that this also happens with a set of essential genes that is evolutionarily conserved from flies to humans is fascinating.”
The study found that SMCHD1 in the egg, which persists for only two days after conception, has lifelong effects.
SMCHD1 variants are associated with the developmental disorder Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy (FSHD), a form of muscular dystrophy. The researchers say their findings could have implications for women with SMCHD1 variants and their children in the future.
Drug discovery efforts at WEHI are now using the SMCHD1 knowledge the team has developed to develop new treatments for developmental disorders such as Prader-Willi syndrome and the degenerative disease FSHD.
The research was supported by the NHMRC, a Bellberry-Viertel Senior Medical Research Fellowship, the Victorian Government and the Australian Government. WEHI Contributors: Natalia Benetti, Quentin Guy, Andres Tapia del Fierro, Tamara Beck, Kelsey Breslin, Andrew Kenery, Marnie Blewitt.