The symbiotic relationship between cnidarians and dinoflagellates is one of the most widespread endosymbiosis in our oceans and provides the ecological basis of coral-reef ecosystems. Although several studies have been undertaken to unravel the molecular mechanisms underlying these symbioses, we still know very little about the epigenetic mechanisms that control the transcriptional responses to symbiosis. Using the model organism Exaiptasia diaphana, we show that host genes involved in the regulation of symbiosis are controlled through the association with several activating histone modifications. Further, we find that genes associated with activating histone marks H3K27ac, H3K4me3, H3K9ac and H3K36me3 exhibit higher expression. While genes associated with the repressive histone mark H3K27me3 show significantly lower expression levels. Integration of genome-wide DNA methylation (CpG) further revealed that colocalization of DNA methylation and activating histone marks significantly correlates with significantly higher expression. Based on these results we propose a model by which histone modifications and DNA methylation interact to control gene expression in response to symbiosis. Our results provide new insights into the mechanisms of prominent histone modifications, and their interaction with DNA methylation in regulating symbiosis in cnidarians.