Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 206-217 |
| Number of pages | 12 |
| Journal | Nature Plants |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2025 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© The Author(s) 2025.
Funding
We thank M. Akhavan and the Broad Stem Cell Research Center Biosequencing core for DNA sequencing; B. Strahl for designing the SDG2 catalytic mutation; M. Gehring for rdd mutant seeds; F. Berger for Arabidopsis H2A.Z antibody; and M. Liu, J. Zhou and C. Ng for technical support. This work was supported by a Bill and Melinda Gates Foundation grant (OPP1125410) to S.E.J. and George G. & Betsy H. Laties Graduate Fellowship in Molecular Plant Biology to S.W. S.E.J. is a Howard Hughes Medical Institute Investigator.
| Funders | Funder number |
|---|---|
| Bill and Melinda Gates Foundation | OPP1125410 |