KDM4A Erases the H3R17me2a Mark, Facilitating Chromosome Condensation

Abstract

Chromosome condensation during mitosis is essential for proper cell division. Histone modifications, particularly the dynamic regulation of active and repressive marks, play a crucial role in this process. However, the mechanisms controlling the temporal interplay between these marks remain unclear. This study revealed the reversible regulation of the active mark H3R17me2a and its interplay with the repressive mark H3K9me3. Early in mitosis, CARM1, which is responsible for H3R17me2a formation, is inactivated, while KDM4A gains arginine demethylase activity to remove H3R17me2a via PKCα-mediated phosphorylation. This demethylation step allows Suv39h1 to facilitate H3K9me3 accumulation, promoting the recruitment of the chromosomal passenger complex and subsequent H3S10 phosphorylation, thus completing chromosome condensation. These findings provide novel insights into the interplay between histone modifications during mitosis and the precise mechanisms governing chromosome dynamics.