真核生物基因组必须精确组织才能发挥其适当的功能,由于基因组拓扑结构影响转录调控,细胞分裂,复制,修复,在其他基本过程中。破坏人类基因组拓扑结构会导致疾病,包括癌症.通过高通量测序(Hi-C)评估基因组组织的染色体构象捕获的出现彻底改变了核基因组拓扑的研究;Hi-C阐明了许多基因组结构,包括染色体区域,活性/沉默染色质隔室,拓扑关联域,和染色质循环。虽然低分辨率热图可以提供对染色体水平接触的重要见解,需要高分辨率的Hi-C数据集来揭示单个基因的折叠原理。特别感兴趣的是模拟人类基因组的生物体的高分辨率染色体构象数据集。这里,我们以高分辨率报告了真菌模型生物的基因组拓扑结构。我们的复合Hi-C数据集,它合并了2个独立的数据集,这些数据集使用监测常染色质(DpnII)和异染色质(MseI)的限制性酶生成,以及我们的DpnII/MseI双摘要数据集,为整个染色体的构象和染色质在单个基因的分辨率的折叠提供精致的细节。在组成性异染色质内,我们观察到强烈但随机的内部联系,而富含激活或抑制组蛋白翻译后修饰的常染色质与组成性异色区相关,提示间室接触形成以调节转录。与此一致,具有受损的异染色质的菌株经历了基因表达的许多变化。我们的高分辨率NeurosporaHi-C数据集是真菌群落的杰出资源,并为高等生物基因组拓扑提供有价值的见解。
The eukaryotic genome must be precisely organized for its proper function, as genome topology impacts transcriptional regulation, cell division, replication, and repair, among other essential processes. Disruptions to human genome topology can lead to diseases, including cancer. The advent of chromosome conformation capture with high-throughput sequencing (Hi-C) to assess genome organization has revolutionized the study of nuclear genome topology; Hi-C has elucidated numerous genomic structures, including chromosomal territories, active/silent chromatin compartments, Topologically Associated Domains, and chromatin loops. While low-resolution heatmaps can provide important insights into chromosomal level contacts, high-resolution Hi-C datasets are required to reveal folding principles of individual genes. Of particular interest are high-resolution chromosome conformation datasets of organisms modeling the human genome. Here, we report the genome topology of the fungal model organism Neurospora crassa at a high resolution. Our composite Hi-C dataset, which merges 2 independent datasets generated with restriction enzymes that monitor euchromatin (DpnII) and heterochromatin (MseI), along with our DpnII/MseI double digest dataset, provide exquisite detail for both the conformation of entire chromosomes and the folding of chromatin at the resolution of individual genes. Within constitutive heterochromatin, we observe strong yet stochastic internal contacts, while euchromatin enriched with either activating or repressive histone post-translational modifications associates with constitutive heterochromatic regions, suggesting intercompartment contacts form to regulate transcription. Consistent with this, a strain with compromised heterochromatin experiences numerous changes in gene expression. Our high-resolution Neurospora Hi-C datasets are outstanding resources to the fungal community and provide valuable insights into higher organism genome topology.