Epigenetic Inheritance May Occur More Often than Previously Thought

New research out of Australia suggests 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. The findings shed new light on a driver of healthy development in embryos that could rewrite understanding of what can be inherited from parents and how life experiences may shape us.

Epigenetics is a rapidly growing 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. While the epigenome can be influenced by the environment, including someone’s diet and exposure to pollutants, these epigenetic changes were thought to be very rarely inherited. 

But a new study led by researchers from WEHI in Melbourne and published in Nature Communications significantly broadens the understanding of which genes have epigenetic information passed from mother to child and which proteins are important for controlling this unusual process. The discovery indicates that epigenetic inheritance may occur more frequently than previously thought.  

“It took us a while to process because our discovery was unexpected,” says Professor Marnie Blewitt, chief investigator and Joint Head of the Epigenetics and Development Division at WEHI.  “Knowing that epigenetic information from the mother can have effects with life-long 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 Professor 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 team 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 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 life-long impact. Variants in SMCHD1 are linked to 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 novel therapies to treat disorders like Prader Willi Syndrome and FSHD.