It’s not all in the genes: do we inherit more


image: Pictured: epigenetic tags (orange and blue) on inactive DNA. Researchers say epigenetic tags could be passed on to offspring more often than previously thought. Still from WEHI.TV animation “X Inactivation and Epigenetics” by Etsuko Uno
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Credit: Still from WEHI.TV animation “X Inactivation and Epigenetics” by Etsuko Uno

A fundamental discovery about a driver of healthy development in embryos could rewrite our understanding of what can be inherited from our parents and how their life experiences can shape us.

The new research suggests that epigenetic information, which is based on DNA and is normally reset between generations, is more frequently passed from mother to offspring than previously thought.

The study, led by researchers from WEHI (Melbourne, Australia), significantly expands our understanding of the genes whose epigenetic information is passed from mother to child and the proteins that are important in controlling this unusual process.

In one look

  • First study to find a protein in the mother’s egg that regulates the epigenetic inheritance of a set of genes essential for the development of normal body structure in mammals.
  • While the epigenome can be influenced by the environment, including diet and exposure to pollutants, these epigenetic changes are very rarely inherited.
  • The discovery transforms our understanding of what can be passed on, indicating that epigenetic inheritance may occur more frequently than previously thought.

Epigenetics is a rapidly growing field of science that studies how our genes are turned on and off to allow a set of genetic instructions to create hundreds of different cell types in our bodies.

Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are not normally passed from parents to offspring.

While a small group of “imprinted” genes can carry epigenetic information from one generation to the next, so far very few other genes have been shown to be influenced by the epigenetic state of the mother.

The new research reveals that the supply of a specific protein in the mother’s egg can affect the genes that determine the skeletal structure of the offspring.

Chief investigator Professor Marnie Blewitt said the results initially surprised the team.

“It took us a while to process because our finding was unexpected,” said Professor Blewitt, co-head of WEHI’s Epigenetics and Development Division.

“Knowing that epigenetic information from the mother can have effects on body structure throughout life is exciting, as it suggests that it happens much more than we realize.

“This could open a Pandora’s box of other inherited epigenetic information.”

The study, led by WEHI in collaboration with Associate Professor Edwina McGlinn of Monash University and the Australian Institute of Regenerative Medicine, is published in Nature Communication.

Amazing discovery

The new research focused on the SMCHD1 protein, an epigenetic regulator discovered by Professor Blewitt in 2008, and Hox genes essential for normal skeletal development.

Hox genes control the identity of each vertebra during embryonic development in mammals, while the epigenetic regulator prevents these genes from being activated too early.

In this study, researchers found that the amount of SMCHD1 in the mother’s egg affects the activity of Hox genes and influences the structuring of the embryo. Without maternal SMCHD1 in the egg, the offspring are born with altered skeletal structures.

First author and PhD researcher Natalia Benetti said this was clear evidence that epigenetic information was inherited from the mother, rather than just a pattern of genetic information.

“Although we have over 20,000 genes in our genome, only this rare subset of about 150 genes imprinted and very few others have been shown to carry epigenetic information from one generation to the next” , Benetti said.

“Knowing that this also happens to a set of essential genes that have been conserved during evolution from flies to humans is fascinating.”

Research has shown that SMCHD1 in the egg, which only persists for two days after conception, has a lifelong impact.

Variants of SMCHD1 are linked to 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.

A drug discovery effort at WEHI is currently leveraging the SMCHD1 knowledge established by the team to design new therapies to treat developmental disorders, such as Prader Willi syndrome and the degenerative disorder FSHD.

The research was supported by the NHMRC, a Bellberry-Viertel Senior Medical Research Fellowship, the Victorian Government and the Australian Government. WEHI authors: Natalia Benetti, Quentin Gouil, Andres Tapia del Fierro, Tamara Beck, Kelsey Breslin, Andrew Keniry, Marnie Blewitt.

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