Department of Physiology, 2 Medical Drive, MD9, National University of Singapore, Singapore 117593, Singapore; Neurobiology/Aging Programme, Life Sciences Institute, Centre for Life Sciences, 28 Medical Drive, Singapore 117456, Singapore.
Department of Physiology, 2 Medical Drive, MD9, National University of Singapore, Singapore 117593, Singapore; Neurobiology/Aging Programme, Life Sciences Institute, Centre for Life Sciences, 28 Medical Drive, Singapore 117456, Singapore; Department of Biomedical Engineering, City College of New York, 160 Convent Ave, New York, NY 10031, United States.
Neurobiol Learn Mem. 2019 Mar;159:1-5. doi: 10.1016/j.nlm.2019.01.013. Epub 2019 Jan 28.
Various epigenetic modifications, including histone lysine methylation, play an integral role in learning and memory. The importance of the histone lysine methyltransferase complex G9a/GLP and its associated histone H3 lysine K9 dimethylation in memory formation and cognition, has garnered the attention of researchers in the past decade. Recent studies feature G9a/GLP as the 'bidirectional regulator of synaptic plasticity', the neural correlate of memory. As the 'title' suggests, G9a/GLP participates in the maintenance of both long-term potentiation (LTP) and long-term depression (LTD). This complex is demonstrated to mostly suppress LTP-related plasticity-related products (PRPs). Notably, our recent paper also shows that G9a/GLP facilitates LTD maintenance in intact hippocampal slices - shedding light on the overlooked influence of epigenetics on LTD. Although the exact mechanisms of G9a/GLP activity regulation in cognition remain elusive, pharmacological inhibition of G9a/GLP presents a new avenue of therapeutic intervention in epigenetic dysfunction-related cognitive deficits.
各种表观遗传修饰，包括组蛋白赖氨酸甲基化，在学习和记忆中起着重要作用。过去十年，研究人员一直关注组蛋白赖氨酸甲基转移酶复合物 G9a/GLP 及其相关的组蛋白 H3 赖氨酸 K9 二甲基化在记忆形成和认知中的作用。最近的研究表明，G9a/GLP 是“突触可塑性的双向调节剂”，是记忆的神经相关性。正如“标题”所示，G9a/GLP 参与维持长时程增强（LTP）和长时程抑制（LTD）。该复合物主要抑制与 LTP 相关的可塑性相关产物（PRPs）。值得注意的是，我们最近的一篇论文还表明，G9a/GLP 有助于完整海马切片中 LTD 的维持——这揭示了表观遗传对 LTD 的忽视影响。尽管 G9a/GLP 在认知中的活性调节的确切机制仍不清楚，但 G9a/GLP 的药理学抑制为表观遗传功能障碍相关认知缺陷的治疗干预提供了新途径。
