What Is the Weight of Epigenetic Inheritance over Generations?

Dear Colleagues,

The phenotypic variation of a given organism and their offspring is generally attributed to genetic variation (DNA sequence mutation), while genetics alone are not sufficient to explain the inheritance of all phenotypes and observations. These phenotypic variabilities could be explained by the multi-gene origin of phenotype or by hereditary epigenetic variation.

Organisms (e.g., mammals) develop from the fertilized egg by very efficient and robust epigenetic programs (formation of organs and specific characters of the species). However, with each generation these programs are erased in the male and female germ cells to re-impose specific gender markings. Defects in the erasure or in the de novo imposition of these marks are revealed by the development of certain diseases. We will refer to the determinants of the formation of the species the epigenetic program of the species (EpS) in order to distinguish it from epigenetic inheritance.

Hereditary epigenetic traits are subtle phenotypic changes that persist from generation to generation in the absence of genetic variation (mutation). These phenotypic changes are reversible (based on observations of organism models in the laboratory), and they vary during generation (in as-yet unpredictable ways) and especially in the absence of inducing factors. Epigenetic heredities can for the moment be identified, followed and explained only in homogeneous and stable genetic contexts. This last point underlines the importance of organism models, especially in animals thanks to their consanguinity, stability and to the possibilities of experimenting over several generations.

Model organisms have clearly helped to demonstrate epigenetic inheritance by non-coding RNAs. Multiple phenotypes have already been observed by inducing variations experimentally and or environmentally as acquired characters etc. There are more phenotypes to be discovered. Indeed, genetics and the environment both contribute to yet unpredictable variations in epigenetic inheritance.

RNA is the vector of epigenetic inheritance, which can be verified by the variation in phenotype induced by changes in the level of the transcripts. To date only a fraction of the coding mRNAs have been recognized to be sensitive to epigenetic variation by non-coding RNAs, and the reason has yet to be explained. Results also indicate that the inducing RNAs can vary by modifications such as cytosine methylation. In the absence of the modification/methylation enzyme (Dnmt2), the cell loses the ability to transmit epigenetic inheritance, while it expresses EpS.

At this point we do not see the evolutionary connection as to how these subtle changes are recorded and fixed in and by EpS. We probably lack the conditions of continuous pressure for the selection, and especially the necessary biological time for the appropriate experiments.

In the immediate future, the questions for molecular biologists relate to how these RNA vectors impose their specificities which last at least two to three generations, and how new phenotypes can be found under epigenetic controls.

Epigenetic inheritance is not all or nothing. It is the modulation of the level of cellular transcripts commonly known as the “rheostat effect”. In other words, how does the germ cell (egg/sperm) assimilate information received from environment and express the hereditary epigenetic change?

This Special Issue is intended to provide an overview of some of the latest results and key findings in the field of epigenetic inheritance of global significance as well as neglected phenotypes. We are pleased to invite you to submit a review article or original research article in this field.

We look forward to receiving your contributions.

Dr. Minoo Rassoulzadegan
Prof. Dr. Francois Cuzin
Prof. Dr. Kenneth B. Marcu
Dr. Serpil Taheri
Guest Editors

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• genetic
• epigenetic
• transcripts variation
• diseases
• model organisms