Concepts, mechanisms and implications of long-term epigenetic inheritance

Many modes and mechanisms of epigenetic inheritance have been elucidated in eukaryotes. Most of them are relatively short-term, generally not exceeding one or a few organismal generations. However, emerging evidence indicates that one mechanism, cytosine DNA methylation, can mediate epigenetic inheritance over much longer timescales, which are mostly or completely inaccessible in the laboratory. Here we discuss the evidence for, and mechanisms and implications of, such long-term epigenetic inheritance. We argue that compelling evidence supports the long-term epigenetic inheritance of gene body methylation, at least in the model angiosperm Arabidopsis thaliana, and that variation in such methylation can therefore serve as an epigenetic basis for phenotypic variation in natural populations.