Genomic responses of DNA methylation and transcript profiles in zebrafish cells upon nutrient deprivation stress

Environmental stress such as nutrient deprivation across multiple fields in nature causes physiological and biochemical changes in organism. Understanding the potential epigenetic modulations to phenotypic variation upon nutrient deprivation stress is crucial for environmental assessments. Here, the methyl-cytosine at single-base resolution was mapped across the whole genome and the methylation patterns and methylation levels coordinated with transcript analysis were systemically elaborated in zebrafish embryonic fibroblast cells under serum starvation stress. The down-regulated genes mainly annotated to the pathways of DNA replication and cell cycle that were consistent with cell physiological changes. Vast differentially methylated regions were identified in genomic chromosome and showed enrichment in the intron and intergenic regions. In an integrated transcriptome and DNA methylation analyses, 135 negatively correlated genes were determined, wherein the hub genes of gins2, cdca5, fbxo5, slc29a2, suv39h1b, and zgc:174160 were predominant responsive to the nutrient condition changes. Besides, nutrient recovery and DNA methyltransferases inhibitor supplements partly rescued cell proliferation with decrease of DNA methylation and reactivation of several depressed genes, implying the possible intrinsic relationships among cell physiological state, mRNA expression, and DNA methylation. Collectively, current study proved the broad role of DNA methylation in governing cellular responses to nutrient deprivation and revealed the epigenetic risk of starvation stress in zebrafish.