Role of nucleosome composition and histone variant exchange in associative learning and memory

核小体组成和组蛋白变体交换在联想学习和记忆中的作用

• 批准号: RGPIN-2015-05115
• 负责人: Zovkic, Iva
• 金额: $ 2.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631478
• 关键词: Role; nucleosome; composition; histone; variant

Memory formation is a process in which fleeting events produce lasting outcomes by altering gene expression. Mechanisms by which the environment affects genes is not well understood, but it involves epigenetic modifications of histone proteins H2A, H2B, H3, and H4, which regulate access to DNA. My work is focused on understanding how histones regulate access to DNA as a method for understanding how memories form. We recently identified histone variants, which replace existing histones and alter access to DNA, as a novel epigenetic regulator of memory. Specifically, we found that H2A.Z, a variant of histone H2A, is an epigenetic factor that suppress memory through an unknown mechanism. Given its pervasive expression and relevance for memory, we will focus on mechanisms of H2A.Z regulation as an essential step in elucidating the role of histones in mediating lasting changes in behaviour.

记忆的形成是一个过程，在这个过程中，短暂的事件通过改变基因表达产生持久的结果。环境影响基因的机制尚不清楚，但它涉及组蛋白H2A，H2B，H3和H4的表观遗传修饰，这些蛋白调节DNA的访问。我的工作重点是了解组蛋白如何调节DNA的访问，作为理解记忆如何形成的方法。我们最近发现组蛋白变体，取代现有的组蛋白和改变DNA的访问，作为一种新的记忆表观遗传调节因子。具体来说，我们发现组蛋白H2A的一种变体H2A.Z是一种表观遗传因子，通过一种未知的机制抑制记忆。鉴于其普遍的表达和记忆的相关性，我们将重点关注H2A.Z调节机制，作为阐明组蛋白在介导持久的行为变化中的作用的重要步骤。