Dual histone methyl reader zcwpw1 facilitates repair of meiotic double strand breaks in male mice

Mohamed Mahgoub, Jacob Paiano, Melania Bruno, Wei Wu, Sarath Pathuri, Xing Zhang, Sherry Ralls, Xiaodong Cheng, Andre Nussenzweig, Todd Macfarlan

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9, as an essential meiotic recombination factor required for efficient repair of PRDM9-dependent DSBs and for pairing of homologous chromosomes in male mice. In sum, our results indicate that the evolution of a dual histone methylation writer/reader (PRDM9/ZCWPW1) system in vertebrates remodeled genetic recombination hotspot selection from an ancestral static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.

Original languageEnglish (US)
Article numbere53360
JournaleLife
Volume9
DOIs
StatePublished - Apr 2020

Keywords

  • CUT&RUN
  • Co-evolution
  • DNA double-strand breaks
  • Dual Histone Reader
  • END-seq
  • Meiotic recombination
  • PRDM9
  • Synapsis
  • ZCWPW1

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology

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