Gene body methylation suppresses intragenic transcription and permits epigenetic inheritance in a cnidarian

Gene body methylation (gbM) has been hypothesized to stabilize gene expression, suppress intragenic transcription, or mediate environmental responses, yet direct experimental evidence for its function remains limited. Here, we use the cnidarian Nematostella vectensis to demonstrate that loss of DNA methylation results in viable embryos with only mild effects on gene expression.

Instead, methylation depletion leads to extensive aberrant accessibility and spurious transcriptional initiation, particularly associated to transposable elements within normally methylated gene bodies. This supports a model in which gbM suppresses cryptic regulatory activity in broadly transcribed regions. We further show that abnormal methylation patterns are partially restored in the germline, with recovery biased toward transcriptionally active regions and excluded from repressive chromatin.