Histone H3 lysine 4 methylation recruits DNA demethylases to enforce gene expression in Arabidopsis
Patterning of DNA methylation in eukaryotic genomes is controlled by de novo methylation, maintenance mechanisms and demethylation pathways. In Arabidopsis thaliana, DNA demethylation enzymes are clearly important for shaping methylation patterns, but how they are regulated is poorly understood. Here we show that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and also erased CG DNA methylation in many other regions of the Arabidopsis genome. This methylation erasure was completely blocked in the ros1 dml2 dml3 triple mutant lacking DNA demethylation enzymes, showing that H3K4me3 promotes the active removal of DNA methylation. Conversely, we found that the targeted removal of H3K4me3 increased the efficiency of targeted DNA methylation. These results highlight H3K4me3 as a potent anti-DNA methylation mark and also pave the way for development of more powerful epigenome engineering tools.
Authors
- James Akira Wohlschlegel (ORCID: https://orcid.org/0000-0003-3399-901X)
- Basudev Ghoshal (ORCID: https://orcid.org/0000-0003-1387-0139)
- Jason Gardiner (ORCID: https://orcid.org/0000-0001-9387-6383)
- Steven E. Jacobsen (ORCID: https://orcid.org/0000-0001-9483-138X)
- Ashot Papikian (ORCID: https://orcid.org/0000-0002-2801-6341)
- Yasaman Jami‐Alahmadi (ORCID: https://orcid.org/0000-0001-8289-2222)
- Zhenhui Zhong (ORCID: https://orcid.org/0000-0002-8438-0375)
- Yan He (ORCID: https://orcid.org/0000-0003-3640-8502)
- Suhua Feng (ORCID: https://orcid.org/0000-0001-6048-0083)
- Ming Wang (ORCID: https://orcid.org/0000-0002-1223-3421)
- Shuya Wang (ORCID: https://orcid.org/0000-0001-9850-4634)
Institutions
- Salk Institute for Biological Studies (US)
- Agriculture and Agri-Food Canada (CA)
- Howard Hughes Medical Institute (US)
- University of California, Los Angeles (US)
- Utrecht University (NL)
- Chinese Academy of Sciences (CN)
- Sichuan University (CN)
- Broad Center (US)
- Institute of Zoology (CN)
- State Key Laboratory of Hydraulics and Mountain River Engineering
Publication Details
- Journal
- Nature Plants
- Published
- 2025-02-11
- DOI
- https://doi.org/10.1038/s41477-025-01924-y
- Citations
- 25
- Primary Topic
- Plant Molecular Biology Research
- Type
- article
- Field-Weighted Citation Impact
- 43.75
Funders
- Howard Hughes Medical Institute
- Bill and Melinda Gates Foundation