Gene body methylation acts as a genome defense and enables heritable regulatory variation in a cnidarian

In the cnidarian Nematostella vectensis, gene body methylation (gbM) marks stably expressed genes and is not a driver of dynamic transcription. Loss of 5mC via a DNMT1 inhibitor or DNMT1/UHRF1 morpholinos leads to global demethylation, widespread chromatin opening, and ectopic intragenic transcription, including activation of young transposons. Importantly, methylation is selectively re-established in the germline and is not globally reset after fertilization, allowing heritable aberrant methylation states and generating regulatory variation across generations—supporting gbM as an ancient genome defense in animals.