High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope
Tyagi S, Capitanio JS, Xu J, Chen F, Sharma R, Huang J, Hetzer M. 2023. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. eLife.
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Journal Article
| Epub ahead of print
| English
Author
Tyagi, Swati;
Capitanio, Juliana S.;
Xu, Jiawei;
Chen, Fei;
Sharma, Rahul;
Huang, Jialiang;
Hetzer, MartinISTA 
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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.
Publishing Year
Date Published
2023-06-23
Journal Title
eLife
Acknowledgement
This work was supported by M.H.’s NIH R01 grants (NS096786, GM126829) and Salk Cancer Center Support Grant P30 CA014195. M.H. also received financial support from the W.M. Keck Foundation and the NOMIS Foundation. Further, M.H. received support from the AHA-Allen Initiative in Brain Health and Cognitive Impairment award made jointly through the American Heart Association and The Paul G. Allen Frontiers Group (19PABH134610000).
S.T. and J.C. were supported by Salk’s Women & Science Awards. S.T. also received financial support from the Hewitt Foundation fellowship, and J.C. is a Paul F. Glenn Biology of Aging fellow. J.H. was supported by the National Natural Science Foundation of China (31871317 and 32070635).
We thank Roberta Schulte for assistance with in vitro transport assays, for comments that greatly improved the manuscript, and for helping refine the figures presented in this work. We thank Shefali Krishna for creating the diagram for the NPC-DamID method, for her input on super-resolution microscopy analysis, and her insightful comments on this manuscript. We thank all members of the Hetzer lab for helpful discussions of these research ideas and their thoughtful comments on this manuscript. We are also grateful to Salk’s core facilities for their assistance. Specifically, we thank the Next Generation Sequencing Core (NGS) for sequencing our DamID and RNA NGS libraries, the Advanced Biophotonics Core for assistance with super-resolution microscopy, and the Razavi Newman Integrative Genomics and Bioinformatics Core (IGC) for their input on analysis methods for DamID experiments.
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Cite this
Tyagi S, Capitanio JS, Xu J, et al. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. eLife. 2023. doi:10.7554/elife.87462
Tyagi, S., Capitanio, J. S., Xu, J., Chen, F., Sharma, R., Huang, J., & Hetzer, M. (2023). High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.87462
Tyagi, Swati, Juliana S. Capitanio, Jiawei Xu, Fei Chen, Rahul Sharma, Jialiang Huang, and Martin Hetzer. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” ELife. eLife Sciences Publications, 2023. https://doi.org/10.7554/elife.87462.
S. Tyagi et al., “High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope,” eLife. eLife Sciences Publications, 2023.
Tyagi S, Capitanio JS, Xu J, Chen F, Sharma R, Huang J, Hetzer M. 2023. High-precision mapping of nuclear pore-chromatin interactions reveals new principles of genome organization at the nuclear envelope. eLife.
Tyagi, Swati, et al. “High-Precision Mapping of Nuclear Pore-Chromatin Interactions Reveals New Principles of Genome Organization at the Nuclear Envelope.” ELife, eLife Sciences Publications, 2023, doi:10.7554/elife.87462.
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