Supplementary Material. The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer’s disease brain.

Supplementary Material. The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer’s disease brain. Background Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the ANK1 gene in Alzheimer’s disease brain samples. However, no study has specifically examined ANK1 histone modifications in the disease. Methods We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the ANK1 gene in entorhinal cortex from donors with high (N= 59) or low (N=29) Alzheimer’s pathology. Discussion 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 ANK1 gene. Conclusions Our study suggests that the ANK1 gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer’s disease.

补充材料。阿尔茨海默病患者大脑ANK1基因座的组蛋白H3第4位赖氨酸三甲基化（H3K4me3）存在异常。
背景：多项针对DNA甲基化的全表观基因组关联研究已证实，阿尔茨海默病患者脑样本中ANK1基因的DNA甲基化水平存在异常。
然而，目前尚无研究针对该疾病中ANK1基因的组蛋白修饰开展专门探讨。
方法：本研究采用染色质免疫沉淀-定量PCR（chromatin immunoprecipitation-qPCR），对阿尔茨海默病病理负荷较高组（N=59）与较低组（N=29）受试对象的内嗅皮层中ANK1基因内的组蛋白H3第4位赖氨酸三甲基化（H3K4me3）与组蛋白H3第27位赖氨酸三甲基化（H3K27me3）水平进行定量检测。
讨论：本研究证实，作为基因活跃转录标志物的H3K4me3水平出现下调，而作为基因沉默标志物的H3K27me3水平未发生明显变化；H3K4me3水平与ANK1基因特定区域的DNA甲基化水平呈负相关。
结论：本研究表明，阿尔茨海默病患者体内ANK1基因的表观遗传标记存在异常，提示该基因的激活程度有所降低。