28 January 2013

Epigenetic heredity – how, where, when?

The mechanism of inheritance of epigenetic information is revealed

LifeSciencesToday by the University of Cambridge: Scientists discover how epigenetic information could be inheritedA new study by scientists at the University of Cambridge (UK) shows how the experience gained by parents can be passed on to the genes of their offspring.

Understanding the mechanisms of transmission of epigenetic information and its discharge will help in the fight against diseases associated with the accumulation of aberrant epigenetic markers, such as cancer, or for the "rejuvenation" of old cells.

Epigenetics is a system of molecular mechanisms that activate and suppress the expression of our genes, which uses chemical labels known as epigenetic markers. By binding to DNA, epigenetic markers tell cells whether or not to use a particular gene.

The most common epigenetic marker is the methyl group. The binding of methyl groups to DNA during methylation blocks the attachment of proteins to DNA that normally activate genes. As a result, the gene is not expressed.

Scientists have evidence of epigenetic inheritance – the transmission of changes in certain traits to offspring that parents have developed during their lives. For example, there are historical cases of the impact on the health of children and grandchildren of hunger experienced by their parents and grandfathers, possibly due to inheritance of changes in methylation caused by malnutrition.

Nevertheless, it is believed that between generations epigenetic markers are erased in the so–called primordial germ cells (primordial germ cells) - the precursors of sperm and eggs. This "reprogramming" allows all genes to be read "from scratch", posing the question to scientists – how is the mechanism of epigenetic inheritance implemented in this case?

In the course of the study, British scientists found the answer to a question that has been intensively studied over the past 10 years – how does the erasure of DNA methylation markers occur in primordial germ cells? They managed to find out that methyl groups are converted into hydroxymethyl groups, which then gradually disappear during cell division. This process seems to be surprisingly effective, and its result is the "zeroing" of epigenetic information for each new generation. Understanding the mechanism of epigenetic reset can be used in the fight against diseases associated with the accumulation of aberrant epigenetic markers, such as cancer, or to "rejuvenate" old cells.

Nevertheless, the researchers concluded that in some rare cases, methylation markers can "escape" this reprogramming process and thus be passed on to offspring, explaining the mechanism of epigenetic inheritance. In response to environmental factors such as chemical compounds or nutrition, aberrant gene methylation can occur during an individual's lifetime, leading to abnormal gene expression and the development of diseases. If these labels are inherited by descendants, the expression of their genes may also be pathologically altered.

"Our study explains how genes can store memories of their past experiences, showing that one of the serious objections to the theory of epigenetic inheritance – that epigenetic information is not passed on to the next generation – should be overestimated," says Dr. Jamie Hackett, who led the study. "Apparently, despite the fact that sperm and egg precursors are very effective in removing most methylation markers, they can also be mistaken and, although quite rarely, allow epigenetic information to be passed on to the next generations. Inheritance of characteristic epigenetic information can potentially contribute to the appearance of altered signs or predisposition to diseases in future offspring. However, it is not yet clear what consequences, if any, epigenetic inheritance may have for the human body. Further research should give us a clearer idea of the extent to which hereditary traits may be the result of epigenetic rather than genetic inheritance. This could make a huge difference for future generations."

According to the participant of the study, Professor Azim Surani, this work, firstly, can provide information on how to erase aberrant epigenetic markers that may underlie some diseases. Secondly, it will help to find out whether the impact of environmental factors or nutrition can influence the acquisition of new epigenetic markers by the germ cells of parents, which can avoid erasure and be passed on to subsequent generations with potentially undesirable consequences.

The study was funded by the Wellcome Trust and published in the journal Science:
Hackett et al., Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine.

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