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DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci

View ORCID ProfileYuzhen Liu, Christopher D. McGann, Mary Krebs, Thomas A. Perkins Jr., Rose Fields, View ORCID ProfileConor K. Camplisson, David Z. Nwizugbo, Chris Hsu, View ORCID ProfileShayan C. Avanessian, View ORCID ProfileAshley F. Tsue, View ORCID ProfileEvan E. Kania, View ORCID ProfileDavid M. Shechner, View ORCID ProfileBrian J. Beliveau, View ORCID ProfileDevin K. Schweppe
doi: https://doi.org/10.1101/2024.07.24.604987
Yuzhen Liu
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
3Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA
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Christopher D. McGann
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
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Mary Krebs
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
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Thomas A. Perkins Jr.
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
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Rose Fields
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
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Conor K. Camplisson
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
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David Z. Nwizugbo
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
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Chris Hsu
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
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Shayan C. Avanessian
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
3Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA
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Ashley F. Tsue
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
4Department of Pharmacology, University of Washington, Seattle, WA, USA
5Institute of Stem Cell and Regenerative Medicine, University of Washington, USA
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Evan E. Kania
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
4Department of Pharmacology, University of Washington, Seattle, WA, USA
5Institute of Stem Cell and Regenerative Medicine, University of Washington, USA
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David M. Shechner
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
4Department of Pharmacology, University of Washington, Seattle, WA, USA
5Institute of Stem Cell and Regenerative Medicine, University of Washington, USA
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Brian J. Beliveau
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
5Institute of Stem Cell and Regenerative Medicine, University of Washington, USA
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  • For correspondence: [email protected] [email protected]
Devin K. Schweppe
1Department of Genome Sciences, University of Washington, Seattle, WA, USA
2Brotman Baty Institute for Precision Medicine, Seattle, WA, USA
5Institute of Stem Cell and Regenerative Medicine, University of Washington, USA
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  • For correspondence: [email protected] [email protected]
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Abstract

The accuracy of crucial nuclear processes such as transcription, replication, and repair, depends on the local composition of chromatin and the regulatory proteins that reside there. Understanding these DNA-protein interactions at the level of specific genomic loci has remained challenging due to technical limitations. Here, we introduce a method termed “DNA O-MAP”, which uses programmable peroxidase-conjugated oligonucleotide probes to biotinylate nearby proteins. We show that DNA O-MAP can be coupled with sample multiplexed quantitative proteomics and next-generation sequencing to quantify DNA-protein and DNA-DNA interactions at specific genomic loci.

Competing Interest Statement

D.K.S. is a collaborator with Thermo Fisher Scientific, Genentech, Calico Labs, and AI Proteins. C.K.C., A.F.T., E.K., D.M.S., and B.J.B. have filed a patent application covering aspects of this work. B.J.B. is listed as an inventor on patent applications related to the SABER technology related to this work.

Footnotes

  • Updated Author List to include one more authors and added one more item to the Acknowledgements section.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted July 29, 2024.
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DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci
Yuzhen Liu, Christopher D. McGann, Mary Krebs, Thomas A. Perkins Jr., Rose Fields, Conor K. Camplisson, David Z. Nwizugbo, Chris Hsu, Shayan C. Avanessian, Ashley F. Tsue, Evan E. Kania, David M. Shechner, Brian J. Beliveau, Devin K. Schweppe
bioRxiv 2024.07.24.604987; doi: https://doi.org/10.1101/2024.07.24.604987
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DNA O-MAP uncovers the molecular neighborhoods associated with specific genomic loci
Yuzhen Liu, Christopher D. McGann, Mary Krebs, Thomas A. Perkins Jr., Rose Fields, Conor K. Camplisson, David Z. Nwizugbo, Chris Hsu, Shayan C. Avanessian, Ashley F. Tsue, Evan E. Kania, David M. Shechner, Brian J. Beliveau, Devin K. Schweppe
bioRxiv 2024.07.24.604987; doi: https://doi.org/10.1101/2024.07.24.604987

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