Cell: Challenge the routine! Revealing the new mechanism of epigenetic transmission of epigenetic memory

According to Epigenetics - the study of heritable genetic changes, where such genetic changes are not directly encoded by our DNA - our life experiences may be passed on to our children and our children. child. Studies of survivors of traumatic events have suggested that exposure to stress may indeed continue to affect future generations. But how do these epigenetic "memory" pass?

In a new study, Dr. Oded Rechavi from Tel Aviv University in Israel and his team accurately articulate the mechanisms that allow the environmental impact to “open” and “close”. They reveal rules that determine which epigenetic responses will be inherited and how long. The results of the study were published in the March 24, 2016 issue of Cell , entitled "A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans."

Dr. Rechavi said, “Before this, a passive dilution or decay process was thought to regulate the inheritance of epigenetic responses. But we confirmed that there is an active process that regulates the intergenerational inheritance of epigenetic responses.”

Intergenerational transmission of stress

Researchers have been focusing on how the effects of stress, trauma, and other environmental exposures are passed on to the next generation within a few years. Small RNA molecules -- short RNA sequences that regulate gene expression -- are one of the key factors involved in the regulation of this inheritance. Dr. Rechavi and his team previously identified a "small RNA inheritance" mechanism by which RNA molecules respond to the needs of specific cells and also identify how they are regulated during intergenerational delivery.

Dr. Rechavi said, "We have previously confirmed that nematodes can inherited small RNAs to their offspring after suffering from hunger and viral infection. These small RNAs prepare their offspring for similar suffering. We also identified an amplification The mechanism of small RNA that can be inherited genetically, therefore, this epigenetic reaction will not be diluted. We found that the enzyme RdRP is required to regenerate new small RNAs, and this small RNA regeneration makes this epigenetic The response continues to pass on to the next generation."

Scientists have previously discovered that most heritable epigenetic responses to C. elegans can only be passed on for generations. According to this, scientists speculate that epigenetic effects will only gradually disappear over time through a process of dilution or exhaustion.

Dr. Rechavi said, "But this speculation ignores the possibility that this process will not simply die but will be regulated." In this study, he used targeting to the green fluorescent protein-encoding gene (GFP). The small RNA is processed by Caenorhabditis elegans, where GFP is a frequently used reporter gene in experiments. "By tracking the heritable small RNAs that regulate GFP--these small RNAs that inhibit GFP expression, we uncover an active, tunable genetic mechanism that can 'turn on' or 'close'."

The researchers found that their specific genes, named "MOTEK (Modified Transgenerational Epigenetic Kinetics), are involved in the initiation and closure of epigenetic intergenerational transmission.

Dr. Rechavi said, "We have found out how to manipulate the intergenerational genetic duration of epigenetic responses in nematodes by 'opening' and 'closing' small RNAs that are used to regulate genes. These switches are made up of small heritable regulatory genes. RNA is controlled by the feedback between the MOTEK gene that is required for the generation and delivery of these small RNAs that are inherited across generations."

"This feedback determines whether epigenetic memory continues to pass on to future generations and how long each epigenetic response will last."

A comprehensive genetic theory?

Although the study was conducted on nematodes, the researchers believe that understanding the control of epigenetic information is critical to building a comprehensive genetic theory for all organisms, including humans.

Leah Houri-Zeevi, Ph.D., Ph.D. student of Dr. Rechavi's lab, said, "We are now planning to study the MOTEK gene to know exactly how these genes affect the duration of epigenetic effects. Furthermore, we are planning to study similar Whether the mechanism also exists in humans."