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

Nat Commun. 2018 Aug 28;9(1):3477. doi: 10.1038/s41467-018-05930-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cells, Cultured
  • Female
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Immunoprecipitation
  • Meiosis / genetics
  • Meiosis / physiology
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Oocytes / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Cxxc1 protein, mouse
  • Histones
  • Trans-Activators
  • histone H3 trimethyl Lys4
  • CDC2 Protein Kinase
  • Cdk1 protein, mouse