Abstract
Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the ANK1 gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined ANK1 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 ANK1 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 ANK1 gene. Our study suggests that the ANK1 gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.
Highlights
Our study provides a preliminary exploration of the histone modification profile of the ANK1 gene in Alzheimer’s disease (AD) brain tissue
This study is the first to interrogate H3K4me[3] and H3K27me[3] modification profiles across the ANK1 gene in AD brain tissue. These results suggest that H3K4me[3] levels are reduced in multiple genomic regions in ANK1 in AD EC and are correlated with changes in DNA methylation and hydroxymethylation. These patterns of epigenetic changes, together with increased DNA methylation, would be expected to result in reduced gene activation, which should be fully explored in future studies
Future perspective Since the first Epigenome-wide association studies (EWAS) of DNA methylation in AD, the amount of research exploring the role of epigenetic mechanisms in neurological diseases has increased dramatically
Summary
This study used EC tissue from post-mortem brain samples collected from 88 individuals archived in the MRC London Neurodegenerative Diseases Brain Bank. We had matched genome-wide DNA methylation and hydroxymethylation data generated for 63 of these samples using the Illumina Infinium Human Methylation 450K BeadChip Array (450K array) on bisulfite and oxidative-bisulfite treated DNA samples, which is available from the gene expression omnibus under accession number GSE105109 [5]. A subset of 47 samples had matched ChIP-seq data for the modification H3K27ac [23]. Donors used in the current study had varying degrees of AD pathology, ranging from Braak Stage 0 to Braak Stage VI, and were all over the age of 65 years. All samples were dissected by trained specialists, snap-frozen and stored at -80◦C. Further demographic information about all samples is provided in Supplementary Table 1
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
