New research reveals a potential explanation for how parents’ experiences could be passed to their offspring’s genes. It is thought that between each generation, epigenetic marks are erased in cells called primordial gene cells (PGC), the precursors to sperm and eggs. This reprogramming allows all genes to be read afresh for each new person, leaving scientists to question how epigenetic inheritance could occur.

A new study by a team at the University of Cambridge initially discovered how the DNA methylation marks are erased in mouse PGCs: CpG methylation (5mC) is converted to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. 5hmC is then progressively diluted out as the cells divide. This process is remarkably efficient and seems to reset the genes for each new generation, the scientists explain.

However, they also found that some rare methylation can escape the reprogramming process and can thus be passed on to offspring—revealing how epigenetic inheritance could occur. Aberrant methylation could accumulate at genes during a lifetime in response to environmental factors, such as chemical exposure or nutrition, and can cause abnormal use of genes, leading to disease. If these marks are then inherited by offspring, their genes could also be affected.

“It is not yet clear what consequences, if any, epigenetic inheritance might have in humans,” says Jamie Hackett, Ph.D., who led the research. “Further studies should give us a clearer understanding of the extent to which heritable traits can be derived from epigenetic inheritance, and not just from genes. That could have profound consequences for future generations.”

“The new study has the potential to be exploited in two distinct ways,” adds Azim Surani, Ph.D., principal investigator. “First, the work could provide information on how to erase aberrant epigenetic marks that may underlie some diseases in adults. Second, the study provides opportunities to address whether germ cells can acquire new epigenetic marks through environmental or dietary influences on parents that may evade erasure and be transmitted to subsequent generations, with potentially undesirable consequences.”

The research was published today in the journal Science, in an article titled “Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine”.

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