Fundamental discoveries about the dynamics of healthy embryonic development have the potential to rewrite our understanding of what we can inherit from our parents and how their life experiences shape us. there is.
New research suggests that epigenetic information that sits on DNA and is normally reset between generations is passed on from mother to offspring more frequently than previously thought.
Led by researchers at WEHI (Melbourne, Australia), the study explores which genes carry the epigenetic information passed from mother to child and which proteins are important for controlling this abnormal process. greatly broaden the understanding of
at a glance
- First study to find proteins in maternal eggs that regulate the epigenetic inheritance of a set of genes important for normal mammalian body structure development.
- The epigenome can be influenced by the environment, such as someone’s diet or exposure to pollutants, but these epigenetic changes are rarely inherited.
- The findings change our understanding of what is inherited and show that epigenetic inheritance may occur more frequently than previously thought.
Epigenetics is a rapidly growing scientific field that describes how genes are switched on and off, allowing one set of genetic instructions to create hundreds of different cell types in the body. Investigate whether
Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are not typically passed on from parent to child.
A small group of ‘imprinted’ genes can transmit epigenetic information across generations, but so far other genes have been shown to be affected by maternal epigenetic status. very few.
New research reveals that the supply of specific proteins in a mother’s eggs can affect the genes that drive skeletal patterns in offspring.
Principal Investigator Professor Marnie Blewitt said the findings initially surprised the team.
Professor Blewitt, Co-Head of WEHI’s Epigenetics and Development Division, said:
“Knowing that epigenetic information from the mother can have lifelong effects on body patterning suggests that it is happening much more than previously thought. It’s exciting.
“It could open a Pandora’s box as to 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 for Regenerative Medicine, Nature Communications.
surprising discovery
The new research focuses on the epigenetic regulator protein SMCHD1, discovered by Professor Blewitt in 2008, Hox A gene important for normal skeletal development.
Hox Genes control the identity of each vertebra during mammalian embryonic development, but epigenetic regulators prevent these genes from being activated too early.
In this study, researchers found that the amount of SMCHD1 in the mother’s oocytes affected cellular activity. Hox Affects gene and embryo patterning. In the absence of the mother’s SMCHD1 in the egg, offspring were born with altered skeletal structure.
Lead author and postdoctoral researcher Natalia Benetti says this is clear evidence that epigenetic information was inherited from the mother, rather than just genetic information in the blueprint.
“Our genome has over 20,000 genes, but only a rare subset of about 150 imprinted genes, and very few have been shown to pass epigenetic information from generation to generation. said Benetti.
“It’s interesting to know that this also happens for a set of essential genes that have been evolutionarily conserved from flies to humans.”
This study showed that SMCHD1 in the egg, which lasts only two days after conception, has lifelong effects.
Variants in SMCHD1 have been associated with the developmental disorder Bosma Arhinia microphthalmia syndrome (BAMS) and a form of muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD). The researchers say their findings may have future implications for women with SMCHD1 variants and their children.
Drug discovery efforts at WEHI are now leveraging the knowledge of SMCHD1 established by the team to design novel therapeutics to treat developmental disorders such as Prader-Willi syndrome and the degenerative disorder FSHD.
reference: Benetti N, Guiyu Q, Tapia del Fierro A. The other maternal SMCHD1 controls Hox gene expression and patterning in mouse embryos. Nat Combs2022;13(1):4295. Doi: 10.1038/s41467-022-32057-x.
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