Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute-Florida, Jupiter, FL, USA.
Epigenetics. 2011 Jun;6(6):671-4. doi: 10.4161/epi.6.6.15905. Epub 2011 Jun 1.
Dynamic chromatin remodeling is at the heart of most biological processes including gene transcription, DNA replication and repair, cell differentiation and apoptosis. Chromatin remodeling as a result of covalent histone modifications, including histone acetylation, methylation or SUMOylation, play important roles in these processes. Similarly, direct chemical modification of DNA, most notably DNA methylation, also plays a key role in controlling gene expression and basic aspects of cell biology. Memory, one of the most fundamental of all brain functions, is a complex process involving diverse cellular signaling cascades and coordinated regulation of entire networks of genes. Synaptic plasticity, which is defined as activity-dependent changes in synaptic strength between neurons, provides the cellular basis of memory. The role for covalent histone modifications in synaptic plasticity and in learning and memory has been now been firmly established. In contrast, much less had been known concerning DNA methylation in memory formation and storage. Emerging evidence now suggests that DNA methylation plays a central role in these processes, likely by directly influencing the expression of genes involved in synaptic plasticity.
动态染色质重塑是大多数生物学过程的核心,包括基因转录、DNA 复制和修复、细胞分化和凋亡。组蛋白共价修饰(包括组蛋白乙酰化、甲基化或 SUMO 化)导致的染色质重塑在这些过程中发挥着重要作用。同样,DNA 的直接化学修饰,特别是 DNA 甲基化,也在控制基因表达和细胞生物学的基本方面发挥着关键作用。记忆是所有大脑功能中最基本的功能之一,是一个涉及多种细胞信号级联和整个基因网络协调调控的复杂过程。突触可塑性被定义为神经元之间突触强度的活性依赖性变化,为记忆提供了细胞基础。组蛋白共价修饰在突触可塑性以及学习和记忆中的作用已经得到了明确的证实。相比之下,关于 DNA 甲基化在记忆形成和存储中的作用,人们知之甚少。现在有新的证据表明,DNA 甲基化在这些过程中起着核心作用,可能通过直接影响参与突触可塑性的基因的表达。