Ageing-Related Changes to H3K4me3, H3K27ac, and H3K27me3 in Purified Mouse Neurons
Brandon Signal,
Andrew J. Phipps,
Katherine A. Giles,
Shannon N. Huskins,
Timothy R. Mercer,
Mark D. Robinson,
Adele Woodhouse,
Phillippa C. Taberlay
Affiliations
Brandon Signal
Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Andrew J. Phipps
Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Katherine A. Giles
Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Shannon N. Huskins
Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Timothy R. Mercer
Australian Institute for Bioengineering and Nanotechnology, Corner College and Cooper Roads, Brisbane, QLD 4072, Australia
Mark D. Robinson
SIB Swiss Institute of Bioinformatics, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
Adele Woodhouse
Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Phillippa C. Taberlay
Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia
Neurons are central to lifelong learning and memory, but ageing disrupts their morphology and function, leading to cognitive decline. Although epigenetic mechanisms are known to play crucial roles in learning and memory, neuron-specific genome-wide epigenetic maps into old age remain scarce, often being limited to whole-brain homogenates and confounded by glial cells. Here, we mapped H3K4me3, H3K27ac, and H3K27me3 in mouse neurons across their lifespan. This revealed stable H3K4me3 and global losses of H3K27ac and H3K27me3 into old age. We observed patterns of synaptic function gene deactivation, regulated through the loss of the active mark H3K27ac, but not H3K4me3. Alongside this, embryonic development loci lost repressive H3K27me3 in old age. This suggests a loss of a highly refined neuronal cellular identity linked to global chromatin reconfiguration. Collectively, these findings indicate a key role for epigenetic regulation in neurons that is inextricably linked with ageing.
