Stricker Stefan H, Götz Magdalena
MCN Junior Research Group, Munich Center for Neurosciences, Ludwig-Maximilian-Universität, Munich, Germany.
Physiological Genomics, BioMedical Center, Munich, Germany.
Front Neurosci. 2018 Feb 1;12:5. doi: 10.3389/fnins.2018.00005. eCollection 2018.
The pristine formation of complex organs depends on sharp temporal and spatial control of gene expression. Therefore, epigenetic mechanisms have been frequently attributed a central role in controlling cell fate determination. A prime example for this is the first discovered and still most studied epigenetic mark, DNA methylation, and the development of the most complex mammalian organ, the brain. Recently, the field of epigenetics has advanced significantly: new DNA modifications were discovered, epigenomic profiling became widely accessible, and methods for targeted epigenomic manipulation have been developed. Thus, it is time to challenge established models of epigenetic gene regulation. Here, we review the current state of knowledge about DNA modifications, their epigenomic distribution, and their regulatory role. We will summarize the evidence suggesting they possess crucial roles in neurogenesis and discuss whether this likely includes lineage choice regulation or rather effects on differentiation. Finally, we will attempt an outlook on how questions, which remain unresolved, could be answered soon.
复杂器官的原始形成取决于基因表达在时间和空间上的精确控制。因此，表观遗传机制常被认为在控制细胞命运决定中起核心作用。对此的一个主要例子是最早发现且至今研究最多的表观遗传标记——DNA甲基化，以及最复杂的哺乳动物器官——大脑的发育。最近，表观遗传学领域取得了显著进展：发现了新的DNA修饰，表观基因组分析变得广泛可用，并且开发了靶向表观基因组操作的方法。因此，是时候挑战已有的表观遗传基因调控模型了。在这里，我们综述了关于DNA修饰、它们在表观基因组中的分布及其调控作用的当前知识状态。我们将总结表明它们在神经发生中具有关键作用的证据，并讨论这是否可能包括谱系选择调控或对分化的影响。最后，我们将尝试展望如何能很快回答尚未解决的问题。
