We inherit more epigenetic info than we thought

Friday, 26 August, 2022

We inherit more epigenetic info than we thought

Australian researchers have found that epigenetic information, which sits on top of DNA and is normally reset between generations, is more frequently carried from mother to offspring than previously thought.

Their study, led by the Walter and Eliza Hall Institute (WEHI), significantly broadens our understanding of which genes have epigenetic information passed from mother to child and which proteins are important for controlling this unusual process. The research has been published in the journal Nature Communications.

Epigenetics is a field of science that investigates how our genes are switched on and off to allow one set of genetic instructions to create hundreds of different cell types in our body. Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are normally not passed from parent to offspring.

While a tiny group of ‘imprinted’ genes can carry epigenetic information across generations, until now, very few other genes have been shown to be influenced by the mother’s epigenetic state. The new research reveals that the supply of a specific protein in the mother’s egg can affect the genes that drive skeletal patterning of offspring.

“It took us a while to process because our discovery was unexpected,” Professor Blewitt, Joint Head of WEHI’s Epigenetics and Development Division.

“Knowing that epigenetic information from the mother can have effects with lifelong consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought.

“It could open a Pandora’s box as to what other epigenetic information is being inherited.”

The new research focused on the protein SMCHD1, an epigenetic regulator discovered by Blewitt in 2008, and Hox genes, which are critical 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 soon.

The researchers discovered that the amount of SMCHD1 in the mother’s egg affects the activity of Hox genes and influences the patterning of the embryo. Without maternal SMCHD1 in the egg, offspring were born with altered skeletal structures. First author and WEHI PhD researcher Natalia Benetti said this was clear evidence that epigenetic information had been inherited from the mother, rather than just blueprint genetic information.

“While we have more than 20,000 genes in our genome, only that rare subset of about 150 imprinted genes and very few others have been shown to carry epigenetic information from one generation to another,” Benetti said.

“Knowing this is also happening to a set of essential genes that have been evolutionarily conserved from flies through to humans is fascinating.”

The research showed that SMCHD1 in the egg, which only persists for two days after conception, has a lifelong impact. Variants in SMCHD1 are linked to developmental disorder Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy (FSHD), a form of muscular dystrophy, so the researchers’ 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 novel therapies to treat developmental disorders such as Prader–Willi syndrome and FSHD.

Image caption: SMCHD1 produced by the mother (green) seen remaining in embryos as the cells divide. Researchers have found the effect of SMCHD1 from the mother impacts when Hox genes are activated many days later in development. Image credit: Wanigasuriya et al, eLife 2020.

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