Learning and Age-Related Changes in Genome-wide H2A.Z Binding in the Mouse Hippocampus

作者：Stefanelli Gilda; Azam Amber B; Walters Brandon J; Brimble Mark A; Gettens Caroline P; Bouchard Cannon Pascale; Cheng Hai Ying M; Davidoff Andrew M; Narkaj Klotilda; Day Jeremy J; Kennedy Andrew J^*; Zovkic Iva B^*

来源：Cell Reports, 2018, 22(5): 1124-1131.

DOI：10.1016/j.celrep.2018.01.020

Histone variants were recently discovered to regulate neural plasticity, with H2A.Z emerging as a memory suppressor. Using whole-genome sequencing of the mouse hippocampus, we show that basal H2A.Z occupancy is positively associated with steadystate transcription, whereas learning-induced H2A.Z removal is associated with learning-induced gene expression. AAV-mediated H2A.Z depletionenhanced fear memory and resulted in gene-specific alterations of learning-induced transcription, reinforcing the role of H2A.Z as a memory suppressor. H2A.Z accumulated with age, although it remained sensitive to learning-induced eviction. Learning-related H2A.Z removal occurred at largely distinct genes in young versus aged mice, suggesting that H2A.Z is subject to regulatory shifts in the aged brain despite similar memory performance. When combined with prior evidence of H3.3 accumulation in neurons, our data suggest that nucleosome composition in the brain is reorganized with age.

• 出版日期2018-1-30