Graduate School of Biomedical Sciences, Medical Scientist Training Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Genes (Basel). 2022 Nov 1;13(11):1999. doi: 10.3390/genes13111999.
Non-random spatial organization of the chromosomal material inside the nuclei of brain cells emerges as an important regulatory layer of genome organization and function in health and disease. Here, we discuss how integrative approaches assessing chromatin in context of the 3D genome is providing new insights into normal and diseased neurodevelopment. Studies in primate (incl. human) and rodent brain have confirmed that chromosomal organization in neurons and glia undergoes highly dynamic changes during pre- and early postnatal development, with potential for plasticity across a much wider age window. For example, neuronal 3D genomes from juvenile and adult cerebral cortex and hippocampus undergo chromosomal conformation changes at hundreds of loci in the context of learning and environmental enrichment, viral infection, and neuroinflammation. Furthermore, locus-specific structural DNA variations, such as micro-deletions, duplications, repeat expansions, and retroelement insertions carry the potential to disrupt the broader epigenomic and transcriptional landscape far beyond the boundaries of the site-specific variation, highlighting the critical importance of long-range intra- and inter-chromosomal contacts for neuronal and glial function.
非随机的染色体物质在脑细胞核内的空间组织，是基因组组织和功能在健康和疾病中的一个重要调控层。在这里，我们讨论了综合评估染色质在三维基因组背景下的方法，如何为正常和患病的神经发育提供新的见解。对灵长类动物（包括人类）和啮齿动物大脑的研究证实，神经元和神经胶质中的染色体组织在产前和早期产后发育过程中发生高度动态变化，具有在更广泛的年龄窗口内发生可塑性的潜力。例如，在学习、环境丰富、病毒感染和神经炎症的背景下，来自幼年和成年大脑皮层和海马体的神经元三维基因组在数百个基因座发生染色体构象变化。此外，特定位置的结构性 DNA 变异，如微缺失、重复扩增和逆转录元件插入，有可能破坏更广泛的表观基因组和转录景观，远远超出特定变异的范围，突出了长距离的染色体内和染色体间接触对于神经元和神经胶质功能的重要性。
