Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis

Nat Commun. 2021 Jun 1;12(1):3184. doi: 10.1038/s41467-021-23378-4.


During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin Immunoprecipitation Sequencing
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Disease Models, Animal
  • Female
  • Histone Deacetylase 1 / metabolism
  • Histone Deacetylase 2 / metabolism
  • Humans
  • Infertility, Male / genetics
  • Male
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oocytes / cytology
  • Oocytes / metabolism
  • Pachytene Stage / genetics*
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / metabolism*
  • RNA-Seq
  • Spermatids / cytology*
  • Spermatids / metabolism
  • Spermatogenesis / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Kctd19 protein, mouse
  • Nuclear Proteins
  • Potassium Channels, Voltage-Gated
  • Transcription Factors
  • ZFP541 protein, mouse
  • Hdac1 protein, mouse
  • Hdac2 protein, mouse
  • Histone Deacetylase 1
  • Histone Deacetylase 2