Genome-wide Characterization of Learning- and Age-related Regulation of the Histone Variant H2A.Z

Histone variants were recently identified as novel regulators of memory, but little is known about their function in the brain. Here, I used next-generation sequencing to characterize genome-wide learning- and age-dependent binding of the histone variant H2A.Z in the hippocampus of young and aged mice. At baseline, H2A.Z co-localized with histone modifications indicative of active transcription and its binding levels were positively correlated with basal gene expression. In response to learning, H2A.Z was widely evicted from ~3000 sites in both young and aged mice, but this eviction was minimally correlated with learning-induced gene activity at both ages. In addition, several age differences were observed. Specifically, H2A.Z levels were higher in aged compared to young mice, suggesting that H2A.Z accumulates with age. Moreover, H2A.Z was evicted from a unique set of genes in aged mice, which also had a distinct gene expression profile compared to young mice.M.Sc