Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, 117485, Russia.
Biochemistry (Mosc). 2020 Sep;85(9):994-966. doi: 10.1134/S0006297920090023.
Adaptive long-term changes in the functioning of nervous system (plasticity, memory) are not written in the genome, but are directly associated with the changes in expression of many genes comprising epigenetic regulation. Summarizing the known data regarding the role of epigenetics in regulation of plasticity and memory, we would like to highlight several key aspects. (i) Different chromatin remodeling complexes and DNA methyltransferases can be organized into high-order multiprotein repressor complexes that are cooperatively acting as the "molecular brake pads", selectively restricting transcriptional activity of specific genes at rest. (ii) Relevant physiological stimuli induce a cascade of biochemical events in the activated neurons resulting in translocation of different signaling molecules (protein kinases, NO-containing complexes) to the nucleus. (iii) Stimulus-specific nitrosylation and phosphorylation of different epigenetic factors is linked to a decrease in their enzymatic activity or changes in intracellular localization that results in temporary destabilization of the repressor complexes. (iv) Removing "molecular brakes" opens a "critical time window" for global and local epigenetic changes, triggering specific transcriptional programs and modulation of synaptic connections efficiency. It can be assumed that the reversible post-translational histone modifications serve as the basis of plastic changes in the neural network. On the other hand, DNA methylation and methylation-dependent 3D chromatin organization can serve a stable molecular basis for long-term maintenance of plastic changes and memory.
神经系统功能的适应性长期变化（可塑性、记忆）不在基因组中编写，而是直接与许多基因的表达变化相关，这些基因构成了表观遗传调控。总结关于表观遗传在可塑性和记忆调控中的作用的已知数据，我们想强调几个关键方面。(i) 不同的染色质重塑复合物和 DNA 甲基转移酶可以组织成高级别多蛋白抑制复合物，这些复合物协同作用作为“分子刹车片”，在休息时选择性地限制特定基因的转录活性。(ii) 相关的生理刺激在激活的神经元中诱导一连串的生化事件，导致不同信号分子（蛋白激酶、含 NO 的复合物）向核内易位。(iii) 不同表观遗传因子的刺激特异性亚硝化和磷酸化与它们的酶活性降低或细胞内定位变化有关，导致抑制复合物的暂时不稳定。(iv) 去除“分子刹车片”为全局和局部表观遗传变化打开了“关键时间窗口”，触发特定的转录程序和突触连接效率的调节。可以假设可逆的翻译后组蛋白修饰是神经网络可塑性变化的基础。另一方面，DNA 甲基化和依赖甲基化的 3D 染色质组织可以作为长期维持可塑性变化和记忆的稳定分子基础。
