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Cited by 9Genomics and Chromatin DynamicsDNA Repair MechanismsEpigenetics and DNA Methylation

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An integrated structural model of the DNA damage-responsive H3K4me3 binding WDR76:SPIN1 complex with the nucleosome

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Liu, Xingyu, Zhang, Ying, Wen, Zhihui, Hao, Yan, Banks, Charles A.S., Cesare, Joseph, Bhattacharya, Saikat, Arvindekar, Shreyas, Lange, Jeffrey J., Xie, Yixuan, Garcia, Benjamin A., Slaughter, Brian D., Unruh, Jay R., Viswanath, Shruthi, Florens, Laurence, Workman, Jerry L., Washburn, Michael P.·2024·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.2318601121PMC PMC11331135

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Abstract

Serial capture affinity purification (SCAP) is a powerful method to isolate a specific protein complex. When combined with cross-linking mass spectrometry and computational approaches, one can build an integrated structural model of the isolated complex. Here, we applied SCAP to dissect a subpopulation of WDR76 in complex with SPIN1, a histone reader that recognizes trimethylated histone H3 lysine4 (H3K4me3). In contrast to a previous SCAP analysis of the SPIN1:SPINDOC complex, histones and the H3K4me3 mark were enriched with the WDR76:SPIN1 complex. Next, interaction network analysis of copurifying proteins and microscopy analysis revealed a potential role of the WDR76:SPIN1 complex in the DNA damage response. Since we detected 149 pairs of cross-links between WDR76, SPIN1, and histones, we then built an integrated structural model of the complex where SPIN1 recognized the H3K4me3 epigenetic mark while interacting with WDR76. Finally, we used the powerful Bayesian Integrative Modeling approach as implemented in the Integrative Modeling Platform to build a model of WDR76 and SPIN1 bound to the nucleosome.

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Metadata

Authors
Liu, X., Zhang, Y., Wen, Z., Hao, Y., Banks, C. A. S., Cesare, J., Bhattacharya, S., Arvindekar, S., Lange, J. J., Xie, Y., Garcia, B. A., Slaughter, B. D., Unruh, J. R., Viswanath, S., Florens, L., Workman, J. L., & Washburn, M. P.
Affiliations
  • Stowers Institute for Medical Research (US)
  • Tata Institute of Fundamental Research (IN)
  • Washington University in St. Louis (US)
Corresponding author
Washburn, Michael P.
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2024-08-08
Volume
121
Issue
33
Pages
e2318601121-e2318601121
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.2318601121
PMC
PMC11331135
OpenAlex
W4401417600
Cited by
9
References
5
Citations by year
2026: 2 · 2025: 6
FWCI
1.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
Funders
  • HHS | NIH | National Institute of General Medical Sciences (R35GM118068, R35GM145240)
  • Stowers Institute for Medical Research (None Available)
  • Department of Atomic Energy, Government of India (DAE TIFR RTI 4006)
  • Science Engineering and Research Board, Department of Science and Technology, Government of India (SPG/2020/000475)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
SPIN1, H3K4me3, histone reader, DNA damage response, nucleosome, protein complex structure, cross-linking mass spectrometry, histone methylation

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