Natural variation in DNA methylation homeostasis and the emergence of epialleles

Significance DNA methylation is an important chromatin modification that helps delineate heterochromatin and transcriptional silencing. Mutations that disrupt robust targeting of DNA methylation to heterochromatin result in ectopic DNA methylation on genes that can alter transcription. By examining variation in DNA methylation among hundreds of natural accessions of the model plantArabidopsis thaliana , we found evidence that robust targeting of DNA methylation to heterochromatin is a trait that varies within this species. Plant genotypes that had lower levels of methylation in heterochromatin had more genes with DNA methylation, and these genes were prone to transcriptional silencing. These results reveal that epigenetic alleles can arise as a byproduct of maintaining methylation of heterochromatin-associated DNA.