DNA demethylases constrain multigenerational methylome and transcriptome divergence

Long-term inbreeding of quadruple DNA demethylase Arabidopsis thaliana mutants for nine generations shows methylation gains accumulate, with two-thirds unique to single inbred lines.

• Why it matters: DNA methylation is generally stable across generations, but the multigenerational behavior of competing methylation and demethylation pathways is unclear.
• What they did: The study inbred quadruple DNA demethylase mutant lines and closely related wild-type lines by single-seed descent for nine generations, tracking methylation, transcriptomes, and small RNA profiles.
• The result: In mutant lines, methylation gains progressively reinforced or spread, and each line had hundreds of de novo gains; two-thirds of gains and 85% of de novo loci were line-specific, implying demethylases constrain accessible epigenome and transcriptome space over time.

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