The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer's disease brain

Adam R Smith; Rebecca G Smith; Ruby Macdonald; Sarah J Marzi; Joe Burrage; Claire Troakes; Safa Al-Sarraj; Jonathan Mill; Katie Lunnon

doi:10.2144/fsoa-2020-0161

The histone modification H3K4me3 is altered at the ANK1 locus in Alzheimer's disease brain

Future Sci OA. 2021 Feb 9;7(4):FSO665. doi: 10.2144/fsoa-2020-0161.

Authors

Adam R Smith¹, Rebecca G Smith¹, Ruby Macdonald¹, Sarah J Marzi², Joe Burrage¹, Claire Troakes³, Safa Al-Sarraj³, Jonathan Mill¹, Katie Lunnon¹

Affiliations

¹ University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
² The Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
³ Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.

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.

Keywords: ANK1; Alzheimer's disease; DNA methylation; Epigenetics; H3K27me3; H3K4me3; brain; chromatin modifications; histone modifications.

Abstract

Grants and funding