Transgenerational epigenetic inheritance in plants

Interest in transgenerational epigenetic inheritance has intensified with the boosting of knowledge on epigenetic mechanisms regulating gene expression during development and in response to internal and external signals such as biotic and abiotic stresses. Starting with an historical background of scantily documented anecdotes and their consequences, we recapitulate the information gathered during the last 60 years on naturally occurring and induced epialleles and paramutations in plants. We present the major players of epigenetic regulation and their importance in controlling stress responses. The effect of diverse stressors on the epigenetic status and its transgenerational inheritance is summarized from a mechanistic viewpoint. The consequences of transgenerational epigenetic inheritance are presented, focusing on the knowledge about its stability, and in relation to genetically fixed mutations, recombination, and genomic rearrangement. We conclude with an outlook on the importance of transgenerational inheritance for adaptation to changing environments and for practical applications. This article is part of a Special Issue entitled "Epigenetic control of cellular and developmental processes in plants".     

Transgenerational epigenetic inheritance in health and disease

Over the past century, patterns of phenotypic inheritance have been observed that are not easily rationalised by Mendel's rules of inheritance. Now that we have begun to understand more about non-DNA based, or 'epigenetic', control of phenotype at the molecular level, the idea that the transgenerational inheritance of these epigenetic states could explain non-Mendelian patterns of inheritance has become attractive. There is a growing body of evidence that abnormal epigenetic states, termed epimutations, are associated with disease in humans. For example, in several cases of colorectal cancer, epimutations have been identified that silence the human mismatch repair genes, MLH1 and MSH2. But strong evidence that the abnormal epigenetic states are primary events that occur in the absence of genetic change and are inherited across generations is still absent.     

Transgenerational inheritance of longevity: epigenetic mysteries abound

Transgenerational inheritance of epigenetic characteristics in plants has been reported, whereas nongenetic persistence of complex phenotypes in animals is controversial. A recent report by Anne Brunet and colleagues describes a fascinating example of persistence across generations of extended life span in worm and explores whether epigenetic mechanisms account for the longevity.     

Transgenerational inheritance of acquired epigenetic signatures at CpG islands in mice

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Selected aspects of transgenerational epigenetic inheritance and resetting in plants

Transgenerational epigenetic inheritance (TEI), which is the inheritance of expression states and thus traits that are not determined by the DNA sequence, is often postulated but the molecular mechanisms involved are only rarely verified. This especially applies to the heritability of environmentally induced traits, which have gained interest over the last years. Here we will discuss selected examples of epigenetic inheritance in plants and artificially divide them according to the occurrence of inter-generational resetting. The decision which epigenetic marks are reset and which ones are not is crucial for the understanding of TEI. We will consider examples of epialleles found in natural populations and epialleles induced by genetic and/or environmental factors used in experimental setups.     

The epigenetic calnexin-independent state is induced in response to environmental changes

Yeasts have evolved numerous responsive pathways to survive in fluctuating and stressful environments. The endoplasmic reticulum (ER) is sensitive to adverse conditions, which are detected by response pathways to ensure correct protein folding. Calnexin is an ER transmembrane chaperone acting in both quality control of folding and response to persistent stress. Calnexin is a key protein required for viability in certain organisms such as mammals and the fission yeast Schizosaccharomyces pombe . Nevertheless, S. pombe calnexin-independent (Cin) cells were obtained after transient expression of a particular calnexin mutant. The Cin state is dominant, is stably propagated by an epigenetic mechanism and segregates in a non-Mendelian fashion to the meiotic progeny. The nucleolar protein Cif1p was identified as an inducer of the Cin state in a previous genetic screen. Here, we report the identification of novel inducers isolated in an overexpression genetic screen: pyruvate kinase (Pyk1p) and phosphoglycerate kinase (Pgk1p). Addition of pyruvate, the end product of pyruvate kinase and glycolysis, also induced calnexin independence in a dose-dependent manner. Remarkably, growth in respiration media or cold temperatures induced the appearance of Cin cells at high frequencies. Taken together, our results indicate that the Cin state can be triggered by extracellular changes, suggesting that this state represents an epigenetic adaptative response to environmental modifications.     

Epi-alleles in plants: inheritance of epigenetic information over generations

Epigenetic modification of plant gene and transposon activity, which correlates with their methylation, is often heritable over many generations. Such heritable properties allow conventional genetic linkage analysis to identify the sequences affected in epigenetic variants. Machinery controlling the establishment of the epigenetic state and role of the epigenetic controls in plant development are also discussed.     

Variation in epigenetic inheritance

Changing patterns of DNA methylation may underlie differential gene expression in development. Additional sources of variation in allelic methylation may be introduced by parental differences as well as by gamete of origin.     

Transgenerational plasticity in clonal plants

Transgenerational plasticity has recently been recognized as a mechanism allowing phenotypic adjustments to local conditions to be passed onto sexually produced offspring. Although thus far it has been studied mainly in non-clonal plants, the present paper proposes that transgenerational plasticity is also applicable to asexually generated progeny, and that it can have multiple consequences for clonal plants. Indeed, in clonal plants, local phenotypic adjustment transferred to the next generation—whether produced sexually or asexually—can provide a mechanism that assists the population better exploit spatial heterogeneity. Moreover, this concept provides a framework allowing investigation of how long environmental heterogeneity will affect growth of asexually as well as sexually generated progeny.     

Environmentally induced epigenetic transgenerational inheritance of sperm epimutations promote genetic mutations

A variety of environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. This involves the germline transmission of epigenetic information between generations. Exposure specific transgenerational sperm epimutations have been previously observed. The current study was designed to investigate the potential role genetic mutations have in the process, using copy number variations (CNV). In the first (F1) generation following exposure, negligible CNV were identified; however, in the transgenerational F3 generation, a significant increase in CNV was observed in the sperm. The genome-wide locations of differential DNA methylation regions (epimutations) and genetic mutations (CNV) were investigated. Observations suggest the environmental induction of the epigenetic transgenerational inheritance of sperm epimutations promote genome instability, such that genetic CNV mutations are acquired in later generations. A combination of epigenetics and genetics is suggested to be involved in the transgenerational phenotypes. The ability of environmental factors to promote epigenetic inheritance that subsequently promotes genetic mutations is a significant advance in our understanding of how the environment impacts disease and evolution.