It is known that information that is not contained in the DNA sequence - epigenetic information - can be inherited from the parent to the offspring. However, many questions remain unanswered regarding the extent and mechanisms of such inheritance. In this Review, we consider the evidence for transgenerational epigenetic inheritance via the gametes, including cases of environmentally induced epigenetic changes. The molecular basis of this inheritance remains unclear, but recent evidence points towards diffusible factors, in particular RNA, rather than DNA methylation or chromatin. Interestingly, many cases of epigenetic inheritance seem to involve repeat sequences.

No abstract

RNA-directed DNA methylation, one of several RNA interference-mediated pathways in the nucleus, has been documented in plants and in human cells. Despite progress in identifying the DNA methyltransferases, histone-modifying enzymes and RNA interference proteins needed for RNA-directed DNA methylation, the mechanism remains incompletely understood. We screened for mutants defective in RNA-directed DNA methylation and silencing of a transgene promoter in Arabidopsis thaliana and identified three drd complementation groups. DRD1 is a SNF2-like protein required for RNA-directed de novo methylation. We report here that DRD2 and DRD3 correspond to the second-largest subunit and largest subunit, respectively, of a fourth class of DNA-dependent RNA polymerase (polymerase IV) that is unique to plants. DRD3 is a functionally diversified homolog of NRPD1a or SDE4, identified in a separate screen for mutants defective in post-transcriptional gene silencing. The identical DNA methylation patterns observed in all three drd mutants suggest that DRD proteins cooperate to create a substrate for RNA-directed de novo methylation.

DRD1 is a SWI/SNF-like protein that cooperates with a plant-specific RNA polymerase, Pol IVb, to facilitate RNA-directed de novo methylation and silencing of homologous DNA. Screens to identify endogenous targets of this pathway in Arabidopsis revealed intergenic regions and plant genes located primarily in euchromatin. Many putative targets are near retrotransposon LTRs or other intergenic sequences that encode short RNAs, which might epigenetically regulate adjacent genes. Consistent with this, derepression of a solo LTR in drd1 and pol IVb mutants was accompanied by reduced cytosine methylation and transcriptional upregulation of neighboring sequences. The solo LTR and several other LTRs that flank reactivated targets are associated with euchromatic histone modifications but little or no H3K9 dimethylation, a hallmark of constitutive heterochromatin. By contrast, LTRs of retrotransposons that remain silent in the mutants despite reduced cytosine methylation lack euchromatic marks and have H3K9 dimethylation. We propose that DRD1 and Pol IVb establish a basal level of silencing that can potentially be reversed in euchromatin, and further reinforced in heterochromatin by other proteins that induce more stable modifications.