DNA sequence properties that predict susceptibility to epiallelic switching

Transgenerationally heritable epialleles are defined by the stable propagation of alternative transcriptional states through mitotic and meiotic cell cycles. Given that the propagation of DNA methylation at CpG sites, mediated in Arabidopsis by MET1, plays a central role in epigenetic inheritance, we examined genomewide DNA methylation in partial and complete loss-of-function met1 mutants. We interpreted the data in relation to transgenerational epiallelic stability, which allowed us to classify chromosomal targets of epigenetic regulation into (i) single copy and methylated exclusively at CpGs, readily forming epialleles, and (ii) transposon-derived, methylated at all cytosines, which may or may not form epialleles. We provide evidence that DNA sequence features such as density of CpGs and genomic repetitiveness of the loci predispose their susceptibility to epiallelic switching. The importance and predictive power of these genetic features were confirmed by analyses of common epialleles in natural Arabidopsis accessions, epigenetic recombinant inbred lines (epiRILs) and also verified in rice.