Department of Genetics, Cell Biology and Anatomy, Omaha, Nebraska 68198, USA.
Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
Genome Res. 2024 Oct 29;34(10):1477-1486. doi: 10.1101/gr.278408.123.
The neuronal nucleus houses a meticulously organized genome. Within this structure, genetic material is not simply compacted but arranged into a precise and functional 3D chromatin landscape essential for cellular regulation. This mini-review highlights the importance of this chromatin landscape in healthy neurodevelopment, as well as the diseases that occur with aberrant chromatin architecture. We discuss insights into the fundamental mechanistic relationship between histone modifications, DNA methylation, and genome organization. We then discuss findings that reveal how these epigenetic features change throughout normal neurodevelopment. Finally, we highlight single-gene neurodevelopmental disorders that illustrate the interdependence of epigenetic features, showing how disruptions in DNA methylation or genome architecture can ripple across the entire epigenome. As such, we emphasize the importance of measuring multiple chromatin architectural aspects, as the disruption of one mechanism can likely impact others in the intricate epigenetic network. This mini-review underscores the vast gaps in our understanding of chromatin structure in neurodevelopmental diseases and the substantial research needed to understand the interplay between chromatin features and neurodevelopment.
神经元核内有一个精心组织的基因组。在这个结构中，遗传物质不仅被压缩，而且还被排列成一种精确的、功能性的三维染色质景观，这种景观对细胞调节至关重要。这篇迷你综述强调了这种染色质景观在健康神经发育中的重要性，以及异常染色质结构引起的疾病。我们讨论了组蛋白修饰、DNA 甲基化和基因组组织之间基本的机制关系的重要性。然后我们讨论了揭示这些表观遗传特征如何在正常神经发育过程中发生变化的发现。最后，我们强调了单基因神经发育障碍的研究，这些研究说明了表观遗传特征的相互依赖性，表明 DNA 甲基化或基因组结构的破坏如何在整个表观基因组中扩散。因此，我们强调了测量多个染色质结构方面的重要性，因为一种机制的破坏可能会影响复杂的表观遗传网络中的其他机制。这篇迷你综述强调了我们在神经发育性疾病中对染色质结构理解的巨大差距，以及理解染色质特征与神经发育之间相互作用所需的大量研究。
