CFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes

Trimethylation of histone H3 on lysine-4 (H3K4me3) is associated with gene-regulatory elements, but its transcription-independent function in cell division is unclear. CxxC-finger protein-1 (CFP1) is a major mediator of H3K4 trimethylation in mouse oocytes. Here we report that oocyte-specific knockout of Cxxc1 , inhibition of CFP1 function, or abrogation of H3K4 methylation in oocytes each causes a delay of meiotic resumption as well as metaphase I arrest owing to defective spindle assembly and chromosome misalignment. These phenomena are partially attributed to insufficient phosphorylation of histone H3 at threonine-3. CDK1 triggers cell division–coupled degradation and inhibitory phosphorylation of CFP1. Preventing CFP1 degradation and phosphorylation causes CFP1 accumulation on chromosomes and impairs meiotic maturation and preimplantation embryo development. Therefore, CFP1-mediated H3K4 trimethylation provides 3a permission signal for the G2–M transition. Dual inhibition of CFP1 removes the SETD1–CFP1 complex from chromatin and ensures appropriate chromosome configuration changes during meiosis and mitosis.