School of Human Development and Health, Faculty of Medicine, Institute of Developmental Sciences Building (MP887), University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
Centre for Biological Science, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK.
Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102128. doi: 10.1016/j.plefa.2020.102128. Epub 2020 May 21.
Docosahexaenoic acid (DHA, 22:6n-3) and oleic acid (18:1n-9) can alter the DNA methylation of individual CpG loci in vivo and in vitro, although the targeting mechanism is unknown. We tested the hypothesis that the targeting of altered methylation is associated with putative transcription factor response elements (pTREs) proximal to modified loci. Jurkat cells were treated with 22:6n-3 or 18:1n-9 (both 15 μM) for eight days and DNA methylation measured using the MethylationEPIC 850K array. 1596 CpG loci were altered significantly (508 hypermethylated) by 22:6n-3 and 563 CpG loci (294 hypermethylated) by 18:1n-9. 78 loci were modified by both fatty acids. Induced differential methylation was not modified by the PPARα antagonist GW6471. DNA sequences proximal to differentially methylated CpG loci were enriched in zinc-finger pTREs. These findings suggest that zinc-finger-containing transcription factors may be involved in targeting altered DNA methylation modifying processes induced by fatty acids to individual CpG loci.
二十二碳六烯酸（DHA，22:6n-3）和油酸（18:1n-9）可以在体内和体外改变单个 CpG 位点的 DNA 甲基化，尽管靶向机制尚不清楚。我们检验了这样一种假设，即改变的甲基化的靶向与靠近修饰位点的假定转录因子反应元件（pTREs）相关。用 22:6n-3 或 18:1n-9（均为 15 μM）处理 Jurkat 细胞 8 天，并用 MethylationEPIC 850K 阵列测量 DNA 甲基化。22:6n-3 使 1596 个 CpG 位点显著改变（508 个发生高甲基化），18:1n-9 使 563 个 CpG 位点改变（294 个发生高甲基化）。两种脂肪酸都使 78 个基因座发生改变。差异甲基化不受 PPARα 拮抗剂 GW6471 的影响。靠近差异甲基化 CpG 基因座的 DNA 序列富含锌指 pTRE。这些发现表明，含有锌指的转录因子可能参与将脂肪酸诱导的改变的 DNA 甲基化修饰过程靶向到单个 CpG 基因座。
