A major epigenetic silencer that was thought to be essential for brain function is actually completely optional for mature neurons.
Biologists have long believed that a specific chemical mark called H3K27me3 is required to keep certain genes turned off throughout a person's life. This study found that when this mark is completely removed from mature neurons, the cells continue to function normally. There was almost no change in which genes were active or how the DNA was packaged. This discovery challenges the fundamental idea that adult cells need this specific epigenetic machinery to maintain their identity. It suggests that the brain has other, more robust ways of keeping its genetic instructions in order as we age.
Long-term maintenance of H3K27me3 in postmitotic neurons is dispensable for gene expression regulation
bioRxiv · 10.64898/2026.05.05.722847
Neuronal maturation is associated with extensive changes in gene expression and chromatin organization. However, the molecular mechanisms that control the epigenetic landscape in terminally differentiated neurons remain poorly understood. Here, we show that maturing cerebellar granule cells undergo a striking and specific increase in the levels of the repressive histone modification H3K27me3 across different genomic regions, including individual genes, broad intergenic regions, and gene clusters