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High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope

Hetzer, M. W.; tyagi, s.; Chen, F.; Huang, J.

2021-05-11 molecular biology
10.1101/2021.05.10.443506 bioRxiv
Show abstract

The role of nuclear pore complexes (NPCs) in genome organization remains poorly characterized due to technical limitations in probing genome-wide protein-DNA interactions specific to the nuclear periphery. Here, we developed a new sensitive method, NPC-DamID, which combines in vitro reconstitution of nuclear import and DamID technology. The fixation-free method identifies chromatin interactions at the NPCs in intact nuclei from cells and tissues. We found that NPCs are preferentially associated with common and hierarchically arranged super-enhancers (SEs) across multiple cell types. We also uncovered phase-separated condensates at NPCs that compartmentalize and concentrate transcriptional coactivators and structural proteins at SE-regulated genes. Our results support NPCs as anchoring sites for SE regulatory hubs and cell-type-specific transcriptional control.

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