Epigenetic information is passed on to offspring more often than previously thought

A fundamental discovery about a driver of healthy embryonic development 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 sits on DNA and is normally reset between generations, is passed from mother to offspring more often than previously thought.

The study, led by researchers at WEHI (Melbourne, Australia), greatly expands our understanding of which genes have epigenetic information passed from mother to child and which proteins are important in controlling this unusual process.

With a glance

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

Epigenetics is a rapidly developing field of science that studies how our genes are turned on and off to allow a single set of genetic instructions to create 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 small group of ‘imprinted’ genes can carry epigenetic information across generations, very few other genes have so far been shown to be affected by the mother’s epigenetic state.

The new research reveals that the delivery of a specific protein in the mother’s egg can influence the genes that govern the skeletal pattern of the offspring.

Lead researcher Professor Marnie Blewitt said the findings initially surprised the team.

“It took us a while to process because our discovery was unexpected,” said Professor Blewitt, joint head of the Epigenetics and Development Unit at WEHI.

“It’s exciting to know that epigenetic information from the mother can have lifelong body patterning implications, as it suggests that there’s a lot more going on than we’ve ever thought.”

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

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

An amazing discovery

The new research focuses on the protein SMCHD1, an epigenetic regulator discovered by Professor Blewitt in 2008 and Hawks genes that are critical for normal skeletal development.

Hawks 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 the activity of Hawks genes and affects the patterning of the embryo. Without maternal SMCHD1 in the egg, offspring are born with altered skeletal structures.

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

“Although we have 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.

“It’s fascinating to know that this also happens with a set of core genes that have been evolutionarily conserved from flies to humans.”

The research showed that SMCHD1 in the egg, which lasts only two days after conception, has a lifelong impact.

Variants in SMCHD1 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 may have implications for women with SMCHD1 variants and their children in the future.

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

reference: Benetti N, Gouil Q, Tapia del Fierro A, et al. Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo. Nat Comms. 2022;13(1):4295. doi: 10.1038/s41467-022-32057-x.

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