Gene regulation by DNA methylation is contingent on chromatin accessibility during transgenerational plasticity in the purple sea urchin

Epigenetic processes are proposed to contribute to phenotypic plasticity. In invertebrates, DNA methylation commonly varies across environments and can correlate or causally associate with phenotype, but its role in transcriptional responses to the environment remains unclear. Maternal environments experienced by the sea urchin Strongylocentrotus purpuratus induce 3 - 6x greater differential CpG methylation in offspring larvae relative to larval developmental environments, suggesting a role for DNA methylation in transgenerational plasticity (TGP). However, a negligible association has been observed between differentially methylated and differentially expressed genes. What gene regulatory roles does invertebrate DNA methylation possess under environmental change, if any? We quantified DNA methylation and gene expression in S. purpuratus larvae exposed to different ecologically relevant conditions during gametogenesis (maternal conditioning) or embryogenesis (developmental conditioning). We modeled differential gene expression and differential splicing under maternal conditioning as functions of DNA methylation, incorporating variables for genomic feature and chromatin accessibility. We detected significant interactions between differential methylation, chromatin accessibility, and genic architecture associated with differential expression and splicing. Observed transcriptional responses to maternal conditioning were also 4 - 13x more likely when accounting for interactions between methylation and chromatin accessibility. Our results provide evidence that DNA methylation possesses multiple functional roles during TGP in S. purpuratus, but its effects are contingent upon other genomic and epigenomic states. Singularly unpredictive of transcription, DNA methylation is likely one cog in the epigenomic machinery contributing to environmental responses and phenotypic plasticity in S. purpuratus and other invertebrates.