Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernicke's area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization. We find that genome segregation into active and inactive compartments is greatly reduced in neurons compared to other brain cells. Furthermore, neuronal Hi-C maps reveal strong long-range interactions, forming a specific network of PcG-mediated contacts in neurons that is nearly absent in other brain cells. These interacting loci contain developmental transcription factors with repressed expression in neurons and other mature brain cells. But only in neurons, they are rich in bivalent promoters occupied by H3K4me3 histone modification together with H3K27me3, which points to a possible functional role of PcG contacts in neurons. Importantly, other layers of chromatin organization also exhibit a distinct structure in neurons, characterized by an increase in short-range interactions and a decrease in long-range ones.

中文翻译：

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广泛的长程多梳相互作用和弱区室化是人类神经元 3D 基因组的标志

染色质结构调节基因表达并塑造细胞身份，特别是在神经元细胞中。具体来说，多梳族（PcG）蛋白通过将染色质重组为抑制域来建立和维持神经元细胞类型，抑制域限制命运决定基因的表达并维持神经元中不同的基因表达模式。在这里，我们绘制了从四个人脑韦尼克区分离的神经元和非神经元细胞的 3D 基因组结构，并全面分析了染色质组织的神经元特异性方面。我们发现，与其他脑细胞相比，神经元中基因组分离为活性区室和非活性区室的情况大大减少。此外，神经元 Hi-C 图谱揭示了强烈的长程相互作用，在神经元中形成了 PcG 介导的接触的特定网络，而这在其他脑细胞中几乎不存在。这些相互作用的基因座含有发育转录因子，在神经元和其他成熟脑细胞中表达受到抑制。但仅在神经元中，它们富含由 H3K4me3 组蛋白修饰和 H3K27me3 占据的二价启动子，这表明 PcG 接触在神经元中可能发挥功能作用。重要的是，染色质组织的其他层在神经元中也表现出独特的结构，其特征是短程相互作用的增加和长程相互作用的减少。