Epigenetic silencing governs key biological processes, from flowering time in plants to preventing uncontrolled cell growth that drives cancer in humans.
This fundamental cellular process involves genes being switched off, for example in response to chemical or environmental effects, initiating changes to the character of cells without altering the underlying gene sequence.
If we can understand the detailed molecular mechanisms that lie behind epigenetic silencing, we may be able to breed crops that grow more efficiently and develop therapies that prevent diseases.
The research group of Professor Caroline Dean FRS at the John Innes Centre has made great strides in this influential area of the biological sciences.
Previous research by the group had highlighted the importance of a protein complex PRC2 (Polycomb Repressive Complex 2) in silencing the floral repressor gene FLC. In plants like Arabidopsis thaliana the epigenetic silencing of FLC through winter cold acts as a brake on flowering which enables the plant to transition to flowering in the spring, a process known as vernalization.
In new research which appears in Molecular Cell, researchers used the model plant Arabidopsis thaliana to investigate the functional role of polymerization - a process where proteins form dynamic chain-like clusters. They focused on two proteins - VIN3 and VRN5 - that interact with the PRC2 complex and show that the polymerization properties of these proteins are crucial in helping to switch off the FLC gene.
This important detail adds to our understanding of how epigenetic silencing occurs, and it fits into an emerging picture of protein clustering as a critical theme of gene regulation in plants and animals.
"We show that there is strength in numbers: when the proteins cluster together, it helps them to hold on to packaged DNA – in this case, the region containing the gene that needs to be switched off," explains first author of the study Dr Anna Schulten.
"By showing how these proteins work together to silence a key flowering gene, the research reveals a new layer of control in how plants respond to seasonal changes and offers mechanistic insights into gene regulation."
While this research relates to plants and could be used to genetically fine tune timing of flowering in crops, it also has broader implications because the silencing activity of PRC2 is also found in animals and humans.
In humans abnormalities in PRC2 can lead to various diseases, including cancer, neurodegenerative disorders and developmental defects.
The study, a collaboration with the University of York and MRC LMB in Cambridge, reinforces that plants offer a powerful model for understanding the principles of epigenetic processes which can be applied to all life.
VEL-dependent polymerization maintains the chromatin association of Polycomb proteins for the switch to epigenetic silencing, appears in Molecular Cell.
Image Caption – Strength in numbers – an artistic interpretation of the research created by illustrator and motion designer Awesta Rogh, featured on the journal's cover.
The work was funded by the European Research Council Advanced Grant (EPISWITCH-833254), Wellcome Trust (210654/Z/18/Z), Biotechnology and Biological Sciences Research Council Institute Strategic Programmes (BB/J004588/1 and BB/P013511/1), EPSRC (EP/T00214X/1, EP/T002166/1 and EP/W024063/1) and a Royal Society Professorship (RPR1180002) to Caroline Dean. Marc Fiedler was funded by the Medical Research Council, as part of United Kingdom Research and Innovation (MC_U105192715), and the Wellcome Trust (225217/Z/22/Z) granted to LA Passmore.
