Histone H3K27 methylation states are sequentially catalyzed in cycling cells.

Sequential stepwise methylation maintains H3K27 tri-methylation in Polycomb domains during DNA replication in human cells.

• Why it matters: Understanding how histone modifications are preserved through cell division is crucial for insights into gene regulation and cellular memory in proliferating cells.
• What they did: Using CUT&Tag chromatin profiling, the study tracked H3K27 methylation dynamics in human cells, revealing that tri-methylation is maintained by stepwise methylation after DNA replication, with additional di-methylation occurring at inactive genes hours post-replication, and showing that inhibiting PRC2 slows methylation and increases acetylation during S-phase.
• The result: These findings suggest that the timing of replication and slow methylation processes contribute to the plasticity of developmentally silenced genes, enabling faithful duplication of H3K27 modification patterns in rapidly dividing cells.