A new tool to fine-tune plant genomes without changing their DNA could offer a fast and precise alternative to GM breeding and play a key role in developing resilient crops in response to climate change.
A study led by members of the Chromatin and Memory group at the University of Cambridge has uncovered a new way to reprogramme plant genomes using ‘epigenetic engineering’ to change gene activity without altering the underlying DNA sequence.
Epigenetics is the system that sits on top of the DNA and turns genes on and off. The process works by chemical tags or ‘biological switches’, known as epigenetic marks, attaching to DNA and telling a cell to either use or ignore a particular gene.
The research found that a specific biological switch, H3K4me3, can directly activate genes and encourage genetic recombination – the exchange of genetic material to create DNA with new traits – even in areas of the genome that are normally hard to access.
The work opens the door to non-GM approaches to precisely modify plant characteristics, allowing breeders to transfer useful plant features like disease resistance from wild varieties to elite cultivars.
“Increasing the resilience of crops in response to a changing climate is one of the most pressing problems of the 21st century,” said Associate Professor Jake Harris, Head of the Chromatin and Memory group at the Department of Plant Sciences and last author of the paper.
“This technology could accelerate plant breeding by increasing genetic mixing in regions of the genome that are usually locked down. It could also enable non-GM enhancement of key traits such as disease resistance, stress tolerance, and yield stability,” he said.
The paper was published in the journal ‘Nature Communications’ on 31 October 2025.
H3K4me3 causes fundamental genome changes in plants
Building on the latest advances in genome engineering technologies, the team used CRISPR gene-editing tools to precisely place H3K4me3 at specific points in the genome.
They found that directing this chemical signal to specific genes can turn on normally silent genes, enhance disease resistance by activating defence genes, and increase genetic material exchange (meiotic crossovers) in regions that are normally difficult to reach.
“We were intrigued by the long-standing question of whether histone marks like H3K4me3 actually cause changes in gene activity or merely reflect them,” said Harris. “Advances in CRISPR-based ‘epigenome editing’ made it possible to test this directly, so we built tools to do just that in plants.”
“We engineered a modular CRISPR SunTag system that recruits enzymes capable of depositing H3K4me3 at chosen genomic sites. We then measured changes in gene expression, disease resistance, and recombination using molecular, genetic, and sequencing-based approaches.”
“The study shows that H3K4me3 can directly activate genes and promote genetic recombination when precisely placed using CRISPR tools. It demonstrates that this modification can be causally linked to fundamental genome functions in plants,” he said.
Opening new opportunities to accelerate breeding
The key collaborator for this work was Professor Ian Henderson and his Genetic and Epigenetic Inheritance in Plants group - who the Harris group share lab space with.
“One of the most exciting results in the manuscript is about stimulating crossovers,” said Harris.
Increasing genetic mixing in areas of the genome that rarely recombine or shuffle could be key to speeding up the breeding process for future crop improvement.
“We have Ian Henderson and his lab to thank for this. Without Ian there is no way we would have even thought to test this and would certainly not have been able to design the guide RNAs or test them accordingly.”
“We were surprised by how powerful the modification was at stimulating recombination. With a single guide RNA we could blanket entire megabase-spanning regions, because they were repetitive in nature.”
“It suggests that chromatin marks can actively shape the genomic landscape in ways we hadn’t appreciated before,” he said.
Team effort building on previous research
Harris is keen to emphasis the incredible team effort behind this work, especially the first authors, Dr Jenia Binenbaum, Postdoctoral Research Associate, and Vanda Adamkova, PhD student – both based in the Harris lab.
The study also builds on epigenetic gene regulation work from Steve Jacobsen’s lab at the University of California, Los Angeles (UCLA) where Harris was a postdoctoral researcher until 2021.
“The initial discoveries for this work were made by researchers in Steve Jacobsen’s lab back when I was a postdoc in his group. They found that this H3K4me3 depositing version of SunTag was able to switch a reporter from silent to active – this was a key discovery.”
“When I moved to Cambridge, as my lab was going to focus on these types of marks, Steve kindly let me continue to work on and develop these approaches in my own group.”
In terms of next steps, the team hope to move some of these insights into crop species to test whether similar effects can be achieved in agriculturally important genomes.
“On the research side, we’re exploring other chromatin modifiers that might be even more effective or specific and ways to express them in particular tissues or on demand. It’s an exciting time,” Harris said.
Funding: This work was supported by a Royal Society and the European Research Council.
Reference: Jenia Binenbaum, Vanda Adamkova et al., ‘CRISPR targeting of H3K4me3 activates gene expression and unlocks centromeric crossover recombination in Arabidopsis’. Nature Communications, DOI: 10.1101/2025.02.07.636860
Image: Conceptual 3D rendering of chromosome. Credit: Koto Feja (Getty Images).