Stress memory is an adaptive mechanism that enables organisms to develop resilience in response to environmental changes. Among them, somatic stress memory is an important means for organisms to cope with contemporary repeated stress, and is accompanied by transcription memory. Sulfide is a common environmental pollutant
however, some organisms have adapted to survive in sulfur-rich environments. Urechis unicinctus is a sulfur-tolerant organism that enhances sulfide stress tolerance by establishing a somatic sulfide stress memory mechanism. However, the molecular mechanisms that regulate sulfide stress memory remain unclear. To explore whether epigenetics, which plays a role in the response of organisms to environmental stress, is involved in regulating somatic sulfide stress memory, we performed a combined analysis of DNA methylation and transcriptome data. We found that elevated levels of DNA methylation under repetitive sulfide stress regulated gene expression and resulted in enhanced sulfide stress tolerance in U. unicinctus, a phenomenon verified using DNA methylase inhibitors. Transcriptional memory can be induced in genes related to oxidative stress, regulation of autophagy, and maintenance of protein homeostasis by altering the level of DNA methylation to facilitate sulfide stress acclimation. Our results provide new insights into adaptive mechanisms to cope with environmental fluctuations.