Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.
Curr Opin Neurobiol. 2019 Dec;59:157-163. doi: 10.1016/j.conb.2019.07.001. Epub 2019 Aug 2.
The last two decades have witnessed explosive advances in our understanding as to how the organization of chromatin, the association of DNA with histones and vast numbers of non-histone regulatory proteins, controls the expression of specific genes in brain. Prominent among such regulatory mechanisms are modifications of histones, along with the 'writers,' 'erasers,' and 'readers' of these modifications. Much of the work delineating these mechanisms has contributed to the idea that a 'histone code' may be a central determinant of a gene's activity and its potential to be activated or repressed in response to environmental perturbations (both beneficial and aberrant). Indeed, increasing evidence has demonstrated the significance of histone regulation in neurological plasticity and disease, although we are still at the earliest stages of examining all of the many potential chromatin changes involved. In this short review, we provide an emerging perspective on putative roles for histones, and their combinatorial readouts, in the context of neural plasticity, and we provide a conceptual framework for future mechanistic studies aimed at uncovering causal links between the neural 'histone code' and brain function/disease.
在过去的二十年中，我们对于染色质的组织、DNA 与组蛋白的结合以及大量非组蛋白调控蛋白如何控制大脑中特定基因的表达有了爆炸式的理解。在这些调控机制中，组蛋白的修饰以及这些修饰的“写入器”、“擦除器”和“读取器”尤为突出。阐明这些机制的大部分工作促成了这样一种观点，即“组蛋白密码”可能是基因活性及其对环境扰动（有益和异常）的激活或抑制的一个核心决定因素。事实上，越来越多的证据表明组蛋白调控在神经可塑性和疾病中具有重要意义，尽管我们仍处于研究所有涉及的许多潜在染色质变化的早期阶段。在这篇简短的综述中，我们提供了一个关于组蛋白及其组合读数在神经可塑性背景下的潜在作用的新视角，并为未来旨在揭示神经“组蛋白密码”与大脑功能/疾病之间因果关系的机制研究提供了一个概念框架。
