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. (C) 2020 Elsevier B.V. All rights reserved.

自然界多个领域中诸如营养缺乏等环境胁迫会导致生物体发生生理和生化变化。了解营养缺乏胁迫下对表型变异的潜在表观遗传调控对于环境评估至关重要。在此，在血清饥饿胁迫下的斑马鱼胚胎成纤维细胞中，以单碱基分辨率绘制了甲基胞嘧啶在全基因组的图谱，并系统阐述了与转录分析相协调的甲基化模式和甲基化水平。下调基因主要注释到与细胞生理变化一致的DNA复制和细胞周期通路。在基因组染色体中鉴定出大量差异甲基化区域，并在内含子和基因间区域显示出富集。在整合的转录组和DNA甲基化分析中，确定了135个负相关基因，其中gins2、cdca5、fbxo5、slc29a2、suv39h1b和zgc:174160等关键基因对营养条件变化有显著响应。此外，营养恢复和DNA甲基转移酶抑制剂补充剂通过降低DNA甲基化和重新激活几个受抑制的基因，部分挽救了细胞增殖，这意味着细胞生理状态、mRNA表达和DNA甲基化之间可能存在内在联系。总之，当前研究证明了DNA甲基化在调控细胞对营养缺乏的反应中具有广泛作用，并揭示了斑马鱼饥饿胁迫的表观遗传风险。（C）2020爱思唯尔有限公司。保留所有权利。