Age- and cell-type-specific effects of histone variant H2BE in the brain

Transcription is regulated in part through histone proteins. Histones can be replaced with variant forms that are particularly critical in the brain and accumulate throughout the lifespan. Recent findings demonstrated that the histone variant H2BE regulates chromatin structure, neuronal transcription, and mouse behavior. However, the role of H2BE in other cell types and throughout the lifespan remains unknown. Here, we discovered that H2BE is enriched in astrocytes and accumulates with age in both astrocytes and neurons. Further, we found that H2BE promotes synaptic gene expression in young neurons and astrocytes and is critical in both cell types for proper synaptic function. In aging brains, loss of H2BE similarly affects synaptic genes in neurons but dampens age-related transcriptional changes in both astrocytes and neurons. Lastly, H2BE loss disrupts long-term memory but improves working memory in aging mice. Together, these data link histone variants with aging-related gene-expression changes in both astrocytes and neurons.