Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
BMC Genomics. 2019 Mar 8;20(1):197. doi: 10.1186/s12864-019-5578-4.
The degradation of epigenetic control with age is associated with progressive diseases of ageing, including cancers, immunodeficiency and diabetes. Reduced caloric intake slows the effects of ageing and age-related disease in vertebrates and invertebrates, a process potentially mediated by the impact of caloric restriction on epigenetic factors such as DNA methylation. We used whole genome bisulphite sequencing to study how DNA methylation patterns change with diet in a small invertebrate, the crustacean Daphnia magna. Daphnia show the classic response of longer life under caloric restriction (CR), and they reproduce clonally, which permits the study of epigenetic changes in the absence of genetic variation.
Global cytosine followed by guanine (CpG) methylation was 0.7-0.9%, and there was no difference in overall methylation levels between normal and calorie restricted replicates. However, 333 differentially methylated regions (DMRs) were evident between the normally fed and CR replicates post-filtering. Of these 65% were hypomethylated in the CR group, and 35% were hypermethylated in the CR group.
Our results demonstrate an effect of CR on the genome-wide methylation profile. This adds to a growing body of research in Daphnia magna that demonstrate an epigenomic response to environmental stimuli. Specifically, gene Ontology (GO) term enrichment of genes associated with hyper and hypo-methylated DMRs showed significant enrichment for methylation and acyl-CoA dehydrogenase activity, which are linked to current understanding of their roles in CR in invertebrate model organisms.
随着年龄的增长，表观遗传控制的退化与衰老相关疾病有关，包括癌症、免疫缺陷和糖尿病。减少热量摄入会减缓脊椎动物和无脊椎动物衰老和与年龄相关疾病的发生，这一过程可能是通过热量限制对表观遗传因素（如 DNA 甲基化）的影响来介导的。我们使用全基因组亚硫酸氢盐测序来研究在一种小型无脊椎动物——大型溞（Daphnia magna）中，饮食如何影响 DNA 甲基化模式。大型溞表现出在热量限制（CR）下寿命延长的典型反应，并且它们进行克隆繁殖，这使得在没有遗传变异的情况下可以研究表观遗传变化。
全局胞嘧啶后跟鸟嘌呤（CpG）甲基化率为 0.7-0.9%，正常和热量限制重复组之间的总体甲基化水平没有差异。然而，在过滤后，正常喂养和 CR 重复组之间有 333 个差异甲基化区域（DMRs）明显不同。其中 65%在 CR 组中呈低甲基化，35%在 CR 组中呈高甲基化。
我们的结果表明 CR 对全基因组甲基化谱有影响。这增加了在大型溞中越来越多的研究表明，环境刺激会引起表观基因组的反应。具体而言，与高甲基化和低甲基化 DMR 相关的基因的基因本体论（GO）术语富集显示，甲基化和酰基辅酶 A 脱氢酶活性显著富集，这与目前对无脊椎动物模型生物中 CR 作用的理解有关。
