Alterations in the epigenetic modulation of gene expression have been implicated in several developmental disorders, cancer, and recently, in a variety of mental retardation and complex psychiatric disorders. A great deal of effort is now being focused on why the nervous system may be susceptible to shifts in activity of epigenetic modifiers. The answer may simply be that the mammalian nervous system must first produce the most complex degree of developmental patterning in biology and hardwire cells functionally in place postnatally, while still allowing for significant plasticity in order for the brain to respond to a rapidly changing environment. DNA methylation and histone deacetylation are two major epigenetic modifications that contribute to the stability of gene expression states. Perturbing DNA methylation, or disrupting the downstream response to DNA methylation - methyl-CpG-binding domain proteins (MBDs) and histone deacetylases (HDACs) - by genetic or pharmacological means, has revealed a critical requirement for epigenetic regulation in brain development, learning, and mature nervous system stability, and has identified the first distinct gene sets that are epigenetically regulated within the nervous system. Epigenetically modifying chromatin structure in response to different stimuli appears to be an ideal mechanism to generate continuous cellular diversity and coordinate shifts in gene expression at successive stages of brain development - all the way from deciding which kind of a neuron to generate, through to how many synapses a neuron can support. Here, we review the evidence supporting a role for DNA methylation and histone deacetylation in nervous system development and mature function, and present a basis from which to understand how the clinical use of HDAC inhibitors may impact nervous system function.

中文翻译：

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DNA甲基化和组蛋白脱乙酰基化对神经系统发育的表观遗传调控。

基因表达的表观遗传学调节的改变与几种发育障碍，癌症有关，最近与多种智力低下和复杂的精神疾病有关。现在，大量的精力集中在为什么神经系统可能易受表观遗传修饰子的活性变化影响的问题上。答案可能仅仅是，哺乳动物的神经系统必须首先在生物学上产生功能最复杂的发育模式，并在出生后在功能上产生硬线细胞，同时仍要具有显着的可塑性，以便大脑对快速变化的环境做出反应。DNA甲基化和组蛋白脱乙酰基化是两个主要的表观遗传修饰，它们有助于基因表达状态的稳定性。干扰DNA甲基化 或通过遗传或药理学方法破坏对DNA甲基化的下游反应-甲基CpG结合域蛋白（MBDs）和组蛋白脱乙酰基酶（HDACs）-已显示出对大脑发育，学习和成熟神经系统进行表观遗传调控的关键要求稳定性，并确定了在神经系统中受表观遗传学调控的第一个不同的基因集。表观遗传修饰染色质结构以响应不同的刺激似乎是在大脑发育的连续阶段产生连续细胞多样性并协调基因表达变化的理想机制-从决定生成哪种神经元一直到神经元可以支持的突触。这里，