The histone modification reader ZCWPW1 is required for meiosis prophase I in male but not in female mice

Sci Adv. 2019 Aug 14;5(8):eaax1101. doi: 10.1126/sciadv.aax1101. eCollection 2019 Aug.

Abstract

Meiosis is a specialized type of cell division that creates haploid germ cells and ensures their genetic diversity through homologous recombination. We show that the H3K4me3 reader ZCWPW1 is specifically required for meiosis prophase I progression in male but not in female germ cells in mice. Loss of Zcwpw1 in male mice caused a complete failure of synapsis, resulting in meiotic arrest at the zygotene to pachytene stage, accompanied by incomplete DNA double-strand break repair and lack of crossover formation, leading to male infertility. In oocytes, deletion of Zcwpw1 only somewhat slowed down meiosis prophase I progression; Zcwpw1-/- oocytes were able to complete meiosis, and Zcwpw1-/- female mice had normal fertility until mid-adulthood. We conclude that the H3K4me3 reader ZCWPW1 is indispensable for meiosis synapsis in males but is dispensable for females. Our results suggest that ZCWPW1 may represent a previously unknown, sex-dependent epigenetic regulator of germ cell meiosis in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • DNA Breaks, Double-Stranded
  • DNA End-Joining Repair / genetics*
  • Female
  • Histone Code / genetics*
  • Histones / genetics
  • Infertility, Male / genetics
  • Male
  • Meiotic Prophase I / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oocytes / cytology*
  • Sex Factors
  • Spermatozoa / cytology*

Substances

  • Cell Cycle Proteins
  • Histones
  • Zcwpw1 protein, mouse
  • histone H3 trimethyl Lys4