The role of epigenetics in neurons

What makes me is my memory. Since ancient times, the memory substance of individuals has been one of our greatest mysteries. What we do know now, at least, is that our memories are encoded in the neurons of our brain. Given that the epigenome consists of cellular memory, the epigenome of neurons should encode the memory of individuals. However, the mechanisms of memory formation based on epigenetic regulation in neurons are still unclear. Our laboratory aims to elucidate the memory substance of individuals encoded in the epigenome of neurons.
     We are now mainly focusing on the role of the epigenome in the memory of aging. It has been well known in many tissues that epigenome, mainly DNA methylation, contains information on aging and age-associated decline of the tissues. However, the epigenetic changes in neurons, not the whole brain, have not been elucidated. Here, we comprehensively analyzed ten epigenome modifications on young and aged hippocampal neurons. Our data suggest that dysregulation of H3K27me3, a repressive histone modification catalyzed by Polycomb group proteins, during neuronal aging is associated with susceptibility to the age-associated decline of brain functions, such as the development of neurodegenerative diseases, excess brain inflammation, geriatric epilepsy, and cognitive decline.
     We are also interested in the other context related to the changes in brain function. We recently started to analyze the neuronal epigenome of mice that have experienced social-isolation stress or brain injury on their motor cortex. Through analyzing neuronal epigenome in the mice that undergo unique experiences or psychiatric diseases, our laboratory tries to reveal the neuronal epigenome encoding memory and to manipulate brain function via epigenome editing.