Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Department of Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.
Sci Adv. 2024 Jul 26;10(30):eado5716. doi: 10.1126/sciadv.ado5716.
The three-dimensional (3D) organization of chromatin within the nucleus is crucial for gene regulation. However, the 3D architectural features that coordinate the activation of an entire chromosome remain largely unknown. We introduce an omics method, RNA-associated chromatin DNA-DNA interactions, that integrates RNA polymerase II (RNAPII)-mediated regulome with stochastic optical reconstruction microscopy to investigate the landscape of noncoding RNA -associated chromatin topology for gene equalization to achieve dosage compensation. Our findings reveal that anchors to the target gene transcription end sites (TESs) and spreads in a distinctive boot-shaped configuration, promoting a more open chromatin state for hyperactivation. Furthermore, arches TES to transcription start sites to enhance transcriptional loops, potentially facilitating RNAPII convoying and connecting proximal promoter-promoter transcriptional hubs for synergistic gene regulation. These TESs cluster as compartments, surrounded by inactive domains for coactivation of multiple genes within the territory. In addition, structures gradually form and scaffold for stepwise coactivation in dosage compensation.
染色质在核内的三维（3D）组织对于基因调控至关重要。然而，协调整个染色体激活的 3D 结构特征在很大程度上仍是未知的。我们引入了一种组学方法，即 RNA 相关染色质 DNA-DNA 相互作用，它将 RNA 聚合酶 II（RNAPII）介导的调控组与随机光学重建显微镜相结合，以研究非编码 RNA 相关染色质拓扑的全景，实现基因均等化，以实现剂量补偿。我们的发现揭示了 锚定到靶基因转录末端位点（TESs）并以独特的靴形结构展开，促进了超激活的更开放染色质状态。此外， 拱起 TES 到转录起始位点，以增强转录环，可能有助于 RNAPII 护航并连接近端启动子-启动子转录枢纽，以实现协同基因调控。这些 TES 簇形成 区室，由非活性区域包围，用于在 区域内共同激活多个基因。此外， 结构逐渐形成并作为剂量补偿中逐步共同激活的支架。
