RRC ID 68746
Author Oura S, Koyano T, Kodera C, Horisawa-Takada Y, Matsuyama M, Ishiguro KI, Ikawa M.
Title KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice.
Journal PLoS Genet
Abstract Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice.
Volume 17(5)
Pages e1009412
Published 2021-5-1
DOI 10.1371/journal.pgen.1009412
PMID 33961623
PMC PMC8104389
MeSH Anaphase Animals CRISPR-Cas Systems / genetics Cell Cycle Proteins / deficiency Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cell Nucleus / metabolism Chromosomal Proteins, Non-Histone / deficiency Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Chromosome Pairing Conserved Sequence DNA Damage Evolution, Molecular Fertility / genetics Genes, Essential* Histone Deacetylase 1 / metabolism Male Meiosis* Meiotic Prophase I Metaphase Mice Nuclear Proteins / deficiency Nuclear Proteins / genetics Nuclear Proteins / metabolism* Pachytene Stage Phenotype Spermatids / cytology Spermatocytes / cytology Spermatocytes / metabolism Testis / metabolism Transcription Factors / deficiency Transcription Factors / genetics Transcription Factors / metabolism* Transgenes
IF 5.175
DNA material pClgn1.1_Kctd19-3xHA (RDB19248) pClgn1.1_3xFLAG-Kctd19 (RDB19249)