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CRISPR targeting of H3K4me3 activates gene expression and unlocks centromere-proximal crossover recombination in Arabidopsis

Author

Listed:
  • Jenia Binenbaum

    (University of Cambridge)

  • Vanda Adamkova

    (University of Cambridge)

  • Hannah Fryer

    (University of Cambridge)

  • Linhao Xu

    (University of Cambridge)

  • Nicola Gorringe

    (University of Cambridge)

  • Piotr Włodzimierz

    (University of Cambridge
    Polish Academy of Sciences)

  • Robin Burns

    (University of Cambridge)

  • Ashot Papikian

    (University of California
    Salk Institute for Biological Studies)

  • Steven E. Jacobsen

    (University of California
    University of California)

  • Ian R. Henderson

    (University of Cambridge)

  • C. Jake Harris

    (University of Cambridge)

Abstract

H3K4me3 is a fundamental and highly conserved chromatin mark across eukaryotes, playing a central role in many genome-related processes, including transcription, maintenance of cell identity, DNA damage repair, and meiotic recombination. However, identifying the causal function of H3K4me3 in these diverse pathways remains a challenge, and we lack the tools to manipulate it for agricultural benefit. Here we use the CRISPR-based SunTag system to direct H3K4me3 methyltransferases in the model plant, Arabidopsis thaliana. Targeting of SunTag-SDG2 activates the expression of the endogenous reporter gene, FWA. We show that SunTag-SDG2 can be employed to increase pathogen resistance by targeting the H3K4me3-dependent disease resistance gene, SNC1. Meiotic crossover recombination rates impose a limit on the speed with which new traits can be transferred to elite crop varieties. We demonstrate that targeting of SunTag-SDG2 to low recombining centromeric regions can significantly stimulate proximal crossover formation. Finally, we reveal that the effect is not specific to SDG2 and is likely dependent on the H3K4me3 mark itself, as the orthogonal mammalian-derived H3K4me3 methyltransferase, PRDM9, produces a similar effect on gene expression with reduced off-target potential. Overall, our study supports an instructive role for H3K4me3 in transcription and meiotic recombination and opens the door to precise modulation of important agricultural traits.

Suggested Citation

  • Jenia Binenbaum & Vanda Adamkova & Hannah Fryer & Linhao Xu & Nicola Gorringe & Piotr Włodzimierz & Robin Burns & Ashot Papikian & Steven E. Jacobsen & Ian R. Henderson & C. Jake Harris, 2025. "CRISPR targeting of H3K4me3 activates gene expression and unlocks centromere-proximal crossover recombination in Arabidopsis," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65167-3
    DOI: 10.1038/s41467-025-65167-3
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    References listed on IDEAS

    as
    1. Hua Wang & Zheng Fan & Pavel V. Shliaha & Matthew Miele & Ronald C. Hendrickson & Xuejun Jiang & Kristian Helin, 2023. "Publisher Correction: H3K4me3 regulates RNA polymerase II promoter-proximal pause-release," Nature, Nature, vol. 616(7956), pages 7-7, April.
    2. Lianna M. Johnson & Jiamu Du & Christopher J. Hale & Sylvain Bischof & Suhua Feng & Ramakrishna K. Chodavarapu & Xuehua Zhong & Giuseppe Marson & Matteo Pellegrini & David J. Segal & Dinshaw J. Patel , 2014. "SRA- and SET-domain-containing proteins link RNA polymerase V occupancy to DNA methylation," Nature, Nature, vol. 507(7490), pages 124-128, March.
    3. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Addendum: Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 636(8042), pages 4-4, December.
    4. Hua Wang & Zheng Fan & Pavel V. Shliaha & Matthew Miele & Ronald C. Hendrickson & Xuejun Jiang & Kristian Helin, 2023. "Author Correction: H3K4me3 regulates RNA polymerase II promoter-proximal pause-release," Nature, Nature, vol. 623(7987), pages 8-8, November.
    5. Hua Wang & Zheng Fan & Pavel V. Shliaha & Matthew Miele & Ronald C. Hendrickson & Xuejun Jiang & Kristian Helin, 2023. "H3K4me3 regulates RNA polymerase II promoter-proximal pause-release," Nature, Nature, vol. 615(7951), pages 339-348, March.
    6. Piotr Wlodzimierz & Fernando A. Rabanal & Robin Burns & Matthew Naish & Elias Primetis & Alison Scott & Terezie Mandáková & Nicola Gorringe & Andrew J. Tock & Daniel Holland & Katrin Fritschi & Anette, 2023. "Cycles of satellite and transposon evolution in Arabidopsis centromeres," Nature, Nature, vol. 618(7965), pages 557-565, June.
    7. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
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