Ben Nolan, Timothy E Reznicek, Christopher T Cummings, M Jordan Rowley
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引用次数: 0
Abstract
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.
神经细胞核内有一个组织严密的基因组。在这个结构中,遗传物质并不是简单地压缩,而是排列成一个精确的功能性三维染色质景观,这对细胞调控至关重要。这篇微型综述强调了染色质结构在健康神经发育中的重要性,以及染色质结构异常导致的疾病。我们将讨论组蛋白修饰、DNA 甲基化和基因组组织之间的基本机制关系。然后,我们将讨论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研究结果。最后,我们重点介绍了单基因神经发育障碍,这些障碍说明了表观遗传特征之间的相互依存关系,显示了 DNA 甲基化或基因组结构的破坏是如何波及整个表观遗传组的。因此,我们强调测量多种染色质结构方面的重要性,因为一种机制的破坏很可能会影响错综复杂的表观遗传网络中的其他机制。这篇微型综述强调了我们对神经发育性疾病中染色质结构的理解存在巨大差距,要了解染色质特征与神经发育之间的相互作用还需要进行大量研究。
期刊介绍:
Launched in 1995, Genome Research is an international, continuously published, peer-reviewed journal that focuses on research that provides novel insights into the genome biology of all organisms, including advances in genomic medicine.
Among the topics considered by the journal are genome structure and function, comparative genomics, molecular evolution, genome-scale quantitative and population genetics, proteomics, epigenomics, and systems biology. The journal also features exciting gene discoveries and reports of cutting-edge computational biology and high-throughput methodologies.
New data in these areas are published as research papers, or methods and resource reports that provide novel information on technologies or tools that will be of interest to a broad readership. Complete data sets are presented electronically on the journal''s web site where appropriate. The journal also provides Reviews, Perspectives, and Insight/Outlook articles, which present commentary on the latest advances published both here and elsewhere, placing such progress in its broader biological context.