Department of Psychiatry and SleepWell Research Program, Faculty of Medicine, University of Helsinki and Helsinki University Central Hospital, Biomedicum 1, Haartmaninkatu 8, 00290, Helsinki, Finland.
Genomics and Biobank UnitDepartment of Public Health Solutions, Finnish Institute for Health and Welfare (THL), PO Box 30, 00271, Helsinki, Finland.
Sci Rep. 2021 Feb 3;11(1):2895. doi: 10.1038/s41598-021-82627-0.
The human DNA methylome is responsive to our environment, but its dynamics remain underexplored. We investigated the temporal changes to DNA methylation (DNAme) in relation to recovery from a shift work disorder (SWD) by performing a paired epigenome-wide analysis in an occupational cohort of 32 shift workers (25 men, age = 43.8 ± 8.8 years, 21 SWD cases). We found that the effect of vacation on DNAme was more prominent in the SWD-group as compared to controls, with respect to the amount of significantly differentially methylated positions (DMPs; P < 0.05) 6.5 vs 3.7%, respectively. The vast majority (78%) of these DMPs were hypomethylated in SWD but not in controls (27%) during the work period. The Gene Ontology Cellular component "NMDA glutamate receptor" (P < 0.05) was identified in a pathway analysis of the top 30 genes in SWD. In-depth pathway analyses revealed that the Reactome pathway "CREB phosphorylation through the activation of CaMKII" might underlie the recovery. Furthermore, three DMPs from this pathway, corresponding to GRIN2C, CREB1, and CAMK2B, correlated with the degree of recovery (P < 0.05). Our findings provide evidence for the dynamic nature of DNAme in relation to the recovery process from a circadian disorder, with biological relevance of the emerging pathways.
人类的 DNA 甲基化组对环境有反应，但它的动态变化仍未得到充分探索。我们通过对 32 名轮班工人（25 名男性，年龄=43.8±8.8 岁，21 名轮班工作障碍病例）的职业队列进行配对的全基因组表观遗传分析，研究了与轮班工作障碍（SWD）恢复相关的 DNA 甲基化（DNAme）的时间变化。我们发现，与对照组相比，SWD 组在休假对 DNAme 的影响方面更为显著，差异甲基化位置（DMP）的数量分别为 6.5%和 3.7%（P<0.05）。在工作期间，这些 DMP 中的绝大多数（78%）在 SWD 中呈低甲基化，但在对照组中（27%）则没有。在 SWD 中排名前 30 位基因的通路分析中，鉴定出了基因本体论细胞成分“NMDA 谷氨酸受体”（P<0.05）。深入的通路分析表明，Reactome 通路“通过激活 CaMKII 对 CREB 的磷酸化”可能是恢复的基础。此外，该通路中的三个 DMP，对应于 GRIN2C、CREB1 和 CAMK2B，与恢复的程度相关（P<0.05）。我们的研究结果为与生物钟紊乱恢复过程相关的 DNAme 的动态性质提供了证据，这些新兴通路具有生物学相关性。
