Smith Adam R, Smith Rebecca G, Macdonald Ruby, Marzi Sarah J, Burrage Joe, Troakes Claire, Al-Sarraj Safa, Mill Jonathan, Lunnon Katie
University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
The Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
Future Sci OA. 2021 Feb 9;7(4):FSO665. doi: 10.2144/fsoa-2020-0161.
Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n = 59) or low (n = 29) Alzheimer's disease pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.
多项关于DNA甲基化的全表观基因组关联研究强调了阿尔茨海默病（AD）脑样本中该基因的DNA甲基化改变。然而，尚无研究专门检测该疾病中的组蛋白修饰。我们使用染色质免疫沉淀-qPCR来定量来自阿尔茨海默病病理学程度高（n = 59）或低（n = 29）的供体的内嗅皮质中该基因的组蛋白3赖氨酸4（H3K4me3）和27（H3K27me3）的三甲基化。我们证明了活性基因转录标志物H3K4me3水平降低，而无活性基因标志物H3K27me3无变化。H3K4me3与该基因特定区域的DNA甲基化呈负相关。我们的研究表明，该基因显示出表观遗传标记改变，表明在阿尔茨海默病中基因激活减少。
