Scientists Reveal We Inherit More Than We Thought

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Inheritance, as it relates to genetics, refers to a trait or variants encoded in DNA and transferred from parent to child during reproduction.

The discovery indicates that epigenetic inheritance may occur more frequently than previously believed.

A fundamental discovery regarding a driver of healthy embryonic development could rewrite our understanding of what we can inherit from our parents and how their life experiences shape us. The new study reveals that epigenetic information, which sits on top of DNA and is usually reset between generations, is more often transmitted from mother to child than previously thought.

The research, led by researchers at the Walter and Eliza Hall Institute in Melbourne, Australia, greatly expands our knowledge of the genes whose epigenetic information is passed from mother to offspring and which proteins are essential for controlling this particular process.

Epigenetics is a growing field of science that studies how our genes are turned on and off to allow a set of genetic instructions to produce hundreds of different cell types in our bodies. Environmental factors such as our diet can impact epigenetic changes, but these changes do not alter DNA and are generally not passed from parent to child.

Epigenetic tags

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

Despite the fact that a small subset of “imprinted” genes can pass epigenetic information from one generation to the next, relatively few other genes have so far been shown to be influenced by the epigenetic state of the mother. According to recent research, the supply of a certain protein in the mother’s egg can impact the genes that govern the skeletal structure of children.

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 for 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, was recently published in the journal Nature Communication.

Natalia Benetti and Marnie Blewitt

Natalia Benetti (left) and Professor Marnie Blewitt (right). 1 credit

Amazing discovery

Current research has focused on Hox genes, essential for normal skeletal development, and the SMCHD1 protein, an epigenetic regulator discovered by Professor Blewitt in 2008. During embryonic development in mammals, Hox genes determine the identity of each vertebra, while regulatory epigenetics prevents these genes from being activated too early.

According to the results of this study, the amount of SMCHD1 in the mother’s egg has an impact on the activity of the Hox genes and the structuring of the embryo. Without maternal SMCHD1 in the egg, children are born with altered skeletal structures.

This is clear evidence, according to first author and Ph.D. researcher Natalia Benetti, that epigenetic information rather than just basic genetic information was passed down from the mother.

SMCHD1 embryo

Maternally produced SMCHD1 (green) seen remaining in embryos as cells divide. Researchers found the effect of SMCHD1 from maternal impacts when Hox genes are activated several days later in development. Credit: Wanigasuriya et al. eLife 2020

“Although we have over 20,000 genes in our genome, only this rare subset of around 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 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.

Reference: “Maternal SMCHD1 regulars Hox gene expression and patterning in the mouse embryo” by Natalia Benetti, Quentin Gouil, Andres Tapia del Fierro, Tamara Beck, Kelsey Breslin, Andrew Keniry, Edwina McGlinn and Marnie E. Blewitt, July 25, 2022, Nature Communication.
DOI: 10.1038/s41467-022-32057-x

The study was funded by the NHMRC, a Bellberry-Viertel Senior Medical Research Fellowship, the Victorian Government and the Australian Government.

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