Researchers from Tel Aviv University have revealed laws that dictate epigenetic inheritance other than through DNA

The researchers wanted to know why epigenetic inheritance disappears after several generations. They discovered a way to reset the timer and overcome the forgetting mechanism of the inherited epigenetic responses 

Dr. Oded Ravavi, editor of the study: The findings of the study may lead to a re-examination of the entire inheritance process

The study was published this weekend in the prestigious journal Cell

Researchers from Tel Aviv University have revealed laws that dictate epigenetic inheritance, that is, inheritance that is not through changes in the DNA sequence, over the generations. The study, which was published this weekend in the important journal Cell, was led by Dr. Oded Ravavi from the Department of Neurobiology in the Faculty of Life Sciences and the Segol School of Neuroscience at Tel Aviv University, together with his student Leah Khoury-Zavi.
"Living beings react to their environment by epigenetic changes," explains Dr. Ravavi, "that is, changes that are not changes in the DNA sequences themselves. Unlike genetic changes, which are permanent changes, epigenetic changes are plastic and dynamic. Thus, for example, in response to environmental challenges, molecules called small RNA can block the expression of certain genes in the DNA during the life of the individual organism. Most of these epigenetic responses are deleted in the germ cells, in a process called reprogramming. Because of this deletion of the epigenetic memory, our training in the gym today will not make our children stronger."
Fifty years before Darwin, Jean-Baptiste Lamarck formulated a description of evolution according to which responses to the environment can be passed from generation to generation, but failed to identify the mechanism, among other things because he ignored the same reprogramming in the germ cells. Lamarck mistakenly believed that giraffes had long necks because their ancestors stretched their necks to reach the tall leaves, efforts that bore fruit in the offspring born with longer necks. And although this simplistic view has been proven wrong, new discoveries in recent years indicate that epigenetic inheritance exists, and it is mediated by the transmission of small RNA molecules from generation to generation.
Dr. Rabi's laboratory has previously proven that worms pass on small RNA molecules to their offspring, which contain information about the parents' environment and thus help the next generation survive. The worms in Dr. Raffi's laboratory inherited information about infection with viruses and the nutritional status of their parents. Dr. Raffi's team was also the first to show that specific enzymes, called RdRPs, enable the copying and amplification of the small RNA molecules that are passed down from generation to generation, so that the epigenetic response is not "forgotten" over the generations, but reawakens again and again thanks to these enzymes.
However, until now it was not known why most epigenetic responses are inherited in a small number of generations, usually three to five - the bottleneck of epigenetic inheritance. It was assumed that the epigenetic responses were simply destroyed over time, in a process of dilution. This assumption did not take into account the possibility that the epigenetic process is also controlled. Similarly, until the scientific community became aware of the groundbreaking work of the monk Gregor Mendel at the beginning of the 20th century, that dilution of parental traits was the accepted, and incorrect, explanation for genetic inheritance. In their new study, Dr. Ravavi and his team demonstrated that there are laws that dictate which epigenetic reactions will be "remembered" and which will be "forgotten" by the offspring - and for several generations.
"We discovered an active process, an epigenetic inheritance mechanism that can be turned on and off," says Leah Khouri-Zavi, a student from Dr. Rahabi's lab and a partner in the new research. "We are describing a feed-back process between small RNA molecules, which regulate gene expression and are inherited, and those genes that are required to produce and transmit the small RNA between generations. This feedback determines when an epigenetic memory will be inherited and when it will not, and for how many generations. Once we isolated the relevant genes, genes we called MOTEK genes (MOdified Transgenerational Epigenetic Kinetics genes), we can, in fact, intervene in determining the duration of epigenetic inheritance."
Reset the stopwatch
The researchers discovered that when artificially initiating a certain epigenetic reaction in worms, that is, controlling the action of a specific gene, the "stopwatch" of the mechanism of epigenetic inheritance is essentially reset, so that the inherited epigenetic reactions are not forgotten three to five generations later. By repeatedly activating the mechanism, and by genetically engineering the MOTEK gene group, the researchers were able to double the number of generations affected by the epigenetic response of their parents.
Now the team of Dr. Ravavi intends to examine the mechanisms of epigenetic inheritance in other species as well. "It is possible that similar laws regulate epigenetic inheritance in humans as well," explains Dr. Rahabi, "but time will tell if these are exactly the same mechanisms we identified in the worms. If so, this means a re-examination of the entire inheritance process. For example, it may be that genetic diagnoses of risk groups for various diseases should include not only genomic analysis, i.e. of the DNA sequences, but also analysis of authorized RNA molecules. This will be good news, because we already have clues from current research about ways in which epigenetic inheritance can be inhibited and stimulated throughout the generations."