Zovkic Iva B, Walters Brandon J
Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
Department of Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
Bioessays. 2015 Jun;37(6):596-601. doi: 10.1002/bies.201400223. Epub 2015 Apr 16.
Histone variant exchange is a novel epigenetic regulator of cognition. We speculate that H2A.Z, a variant of canonical histone H2A, exerts unique effects on transcription during distinct stages of memory formation, ultimately acting to maintain memory of previous transcriptional states and poise genes for re-activation. Hippocampus-dependent memory formation is initiated by transient expression of memory-related genes, which support the storage of recently acquired memories. Soon after, memories undergo systems consolidation, which transfers memories from the hippocampus to the cortex for long-term storage, and requires ongoing re-activation of memory-related genes. We speculate that learning-induced H2A.Z eviction from nucleosomes initially contributes to stimulus-induced transcriptional induction needed for the initial process of memory consolidation. During systems consolidation, we speculate that delayed incorporation of H2A.Z into nucleosomes of memory-related genes in the cortex is needed to poise genes for rapid re-activation, thus supporting the long-term process of memory stabilization.
组蛋白变体交换是一种新型的认知表观遗传调节因子。我们推测，作为经典组蛋白H2A变体的H2A.Z，在记忆形成的不同阶段对转录发挥独特作用，最终起到维持先前转录状态的记忆并使基因处于重新激活的准备状态。海马体依赖的记忆形成由记忆相关基因的短暂表达启动，这些基因支持最近获得记忆的存储。不久之后，记忆经历系统巩固，即将记忆从海马体转移到皮层进行长期存储，这需要记忆相关基因持续重新激活。我们推测，学习诱导的H2A.Z从核小体上移除最初有助于记忆巩固初始过程所需的刺激诱导转录诱导。在系统巩固过程中，我们推测需要延迟将H2A.Z掺入皮层中记忆相关基因的核小体，以使基因处于快速重新激活的准备状态，从而支持记忆稳定的长期过程。
