Epigenetic Inheritance: Concepts, Mechanisms and Perspectives

Abstract

Parents’ stressful experiences can influence an offspring’s vulnerability to many pathological conditions, including psychopathologies, and their effects may even endure for several generations. Nevertheless, the cause of this phenomenon has not been determined, and only recently have scientists turned to epigenetics to answer this question. There is extensive literature on epigenetics, but no consensus exists with regard to how and what can (and must) be considered to study and define epigenetics processes and their inheritance. In this work, we aimed to clarify and systematize these concepts. To this end, we analyzed the dynamics of epigenetic changes over time in detail and defined three types of epigenetics: a direct form of epigenetics (DE) and two indirect epigenetic processes—within (WIE) and across (AIE). DE refers to changes that occur in the lifespan of an individual, due to direct experiences with his environment. WIE concerns changes that occur inside of the womb, due to events during gestation. Finally, AIE defines changes that affect the individual’s predecessors (parents, grandparents, etc.), due to events that occur even long before conception and that are somehow (e.g., through gametes, the intrauterine environment setting) transmitted across generations. This distinction allows us to organize the main body of epigenetic evidence according to these categories and then focus on the latter (AIE), referring to it as a faster route of informational transmission across generations—compared with genetic inheritance—that guides human evolution in a Lamarckian (i.e., experience-dependent) manner. Of the molecular processes that are implicated in this phenomenon, well-known (methylation) and novel (non-coding RNA, ncRNA) regulatory mechanisms are converging. Our discussion of the chief methods that are used to study epigenetic inheritance highlights the most compelling technical and theoretical problems of this discipline. Experimental suggestions to expand this field are provided, and their practical and ethical implications are discussed extensively.

Dopamine Receptor D1 Contributes to Cocaine Epigenetic Reprogramming of Histone Modifications in Male Germ Cells

“…In the last years, there has been special interest in the characterization of epigenetic mechanisms during spermatogenesis that control the reprogramming of the paternal genome, due to the possible trans-generational transmission of acquired traits (Lacal and Ventura, 2018;Galan et al, 2019). Epigenetic reprogramming involves histones post-translational modifications (PTMs), DNA methylation, and changes in small non-coding RNAs that modulate gene expression in response to basal transcriptional programs and environmental signals (Jenkins and Carrell, 2012).…”

scGRNom: a computational pipeline of integrative multi-omics analyses for predicting cell-type disease genes and regulatory networks

“…Therefore, integrating such emerging machine learning approaches will potentially enable the identification of additional cross-omic patterns -especially for increasing single cell multi-omics data and providing more comprehensive mechanistic insights in cell-type gene regulation and in linking to disease genes. This means, for example, adding more omics such as methylation data that reflect epigenetic changes which may occur due to wide variations of inherited and environmental factors [108]. At a deeper functional level, variations in methylation have been attributed to alterations in splicing activity, ultimately impacting the regulation and expression of key genes [109].…”

Epigenetic Mechanisms Contribute to Evolutionary Adaptation of Gene Network Activity under Environmental Selection

“…The concepts of epigenetic inheritance and memory are tightly linked and often used interchangeably to refer to non-DNAbased inheritance (Bonduriansky and Day, 2009). While epigenetic inheritance refers to the passage of certain epigenetic marks to the offspring (Lacal and Ventura, 2018), epigenetic memory is defined as the process of establishing and maintaining a heritable transcriptional state (Acar et al, 2005;Kaufmann et al, 2007;Kundu et al, 2007). Work from the van Oudenaarden group (Acar et al, 2005) described transcriptional memory in the yeast galactose (GAL) network by showing that yeast cells ''remember'' whether they were previously exposed to high or low concentrations of galactose.…”