Multigenerational epigenetic inheritance: Transmitting information across generations

Abstract

Inherited epigenetic information has been observed to regulate a variety of complex organismal phenotypes across diverse taxa of life. This continually expanding body of literature suggests that epigenetic inheritance plays a significant, and potentially fundamental, role in inheritance. Despite the important role these types of effects play in biology, the molecular mediators of this non-genetic transmission of information are just now beginning to be deciphered. Here we provide an intellectual framework for interpreting these findings and how they can interact with each other. We also define the different types of mechanisms that have been found to mediate epigenetic inheritance and to regulate whether epigenetic information persists for one or many generations. The field of epigenetic inheritance is entering an exciting phase, in which we are beginning to understand the mechanisms by which non-genetic information is transmitted to, and deciphered by, subsequent generations to maintain essential environmental information without permanently altering the genetic code. A more complete understanding of how and when epigenetic inheritance occurs will advance our understanding of numerous different aspects of biology ranging from how organisms cope with changing environments to human pathologies influenced by a parent's environment.

Keywords: DNA methylation; Epigenetics; Histone methylation; Intergenerational; Non-Mendellian; Non-genetic; Small RNAs; Transgenerational epigenetic inheritance.

Figure 1:. Distinction between inter and transgenerational phenotypes

Numerous different parental (P0) stresses can have multigenerational effects on offspring. Intergenerational effects represent any effect of parental stress on F1 progeny that either directly acts on or is communicated through P0 germ cells or developing F1 embryos in utero. By comparison, all effects that are initiated in the P0 generation and persist into the F3 (or later) generations are transgenerational effects. Effects that are initiated in the P0 generation and persist to the F2 generation are intergenerational if any germ cells of F1 animals have formed in utero when the initiating event/stress was present and transgenerational if no F1 germ cells have formed. These original distinctions between intergenerational and transgenerational effects in F2 progeny are still used as definitions in the literature irrespective of the mechanisms that mediate multigenerational effects in progeny, including cases where such effects might not be transmitted via germ cells. Figure created with BioRender.com.