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.

中文翻译：

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表观遗传调控作为神经系统长期变化的基础：寻找特异性机制

神经系统功能（可塑性、记忆力）的适应性长期变化并未写入基因组，而是与包括表观遗传调控在内的许多基因的表达变化直接相关。总结关于表观遗传学在可塑性和记忆调节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阶多蛋白抑制复合物，它们协同充当“分子刹车片”，选择性地限制特定基因在静止时的转录活性。(ii) 相关生理刺激在激活的神经元中诱导一系列生化事件，导致不同信号分子（蛋白激酶、含 NO 的复合物）到细胞核。(iii) 不同表观遗传因子的刺激特异性亚硝基化和磷酸化与其酶活性的降低或细胞内定位的变化有关，这导致阻遏物复合物的暂时不稳定。(iv) 去除“分子刹车”为全局和局部表观遗传变化打开了一个“关键时间窗口”，触发了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 甲基化和甲基化依赖的 3D 染色质组织可以为长期维持可塑性变化和记忆提供稳定的分子基础。(iii) 不同表观遗传因子的刺激特异性亚硝基化和磷酸化与其酶活性的降低或细胞内定位的变化有关，这导致阻遏物复合物的暂时不稳定。(iv) 去除“分子刹车”为全局和局部表观遗传变化打开了一个“关键时间窗口”，触发了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 甲基化和甲基化依赖的 3D 染色质组织可以为长期维持可塑性变化和记忆提供稳定的分子基础。(iii) 不同表观遗传因子的刺激特异性亚硝基化和磷酸化与其酶活性的降低或细胞内定位的变化有关，这导致阻遏物复合物的暂时不稳定。(iv) 去除“分子刹车”为全局和局部表观遗传变化打开了一个“关键时间窗口”，触发了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 甲基化和甲基化依赖的 3D 染色质组织可以为长期维持可塑性变化和记忆提供稳定的分子基础。