Department of Psychology, University of Toronto Mississauga, Canada.
Curr Opin Neurobiol. 2021 Apr;67:58-65. doi: 10.1016/j.conb.2020.08.007. Epub 2020 Sep 6.
Nearly two decades of research on epigenetic mechanisms in the brain have demonstrated that epigenetic marks that were once thought to be relatively static are dynamically and reversibly regulated in the brain during memory formation. Here, we focus on new research that has further expanded the dynamic nature of chromatin in memory formation through three key mechanisms. First, we discuss the emerging role of histone variants, which undergo learning-induced turnover or exchange, a process in which one histone type replaces another in chromatin. Next, we focus on chromatin remodeling complexes, which are tightly intertwined with all aspects of chromatin regulation and as such, can reposition or evict nucleosomes to promote transcriptional induction, and mediate histone variant exchange. Finally, we discuss how differential distribution of histone marks to localized narrow genomic regions and/or broadly distributed chromatin domains impact transcriptional outcomes and memory formation. Together, these studies mark a shift toward unraveling the complexity of chromatin function in memory and offer new strategies for fine tuning transcriptional outcomes to modify longevity, specificity and strength of memories.
近二十年的大脑表观遗传机制研究表明，在记忆形成过程中，曾经被认为相对稳定的表观遗传标记在大脑中是动态且可逆调节的。在这里，我们重点介绍了通过三种关键机制进一步扩展了染色质在记忆形成中动态性质的新研究。首先，我们讨论了组蛋白变体的新兴作用，组蛋白变体经历学习诱导的更替或交换，即一种组蛋白类型取代染色质中的另一种组蛋白类型的过程。接下来，我们专注于染色质重塑复合物，它与染色质调节的各个方面紧密交织，因此可以重新定位或逐出核小体以促进转录诱导，并介导组蛋白变体交换。最后，我们讨论了组蛋白标记如何差异分布到局部狭窄的基因组区域和/或广泛分布的染色质域，从而影响转录结果和记忆形成。总的来说，这些研究标志着人们开始揭示染色质在记忆中的功能复杂性，并提供了新的策略来微调转录结果，以改变记忆的寿命、特异性和强度。
