Maintenance DNA methylation in pre-meiotic germ cells regulates meiotic prophase by facilitating homologous chromosome pairing

Yuki Takada, Ruken Yaman-Deveci, Takayuki Shirakawa, Jafar Sharif, Shin Ichi Tomizawa, Fumihito Miura, Takashi Ito, Michio Ono, Kuniko Nakajima, Yoko Koseki, Fuyuko Shiotani, Kei Ichiro Ishiguro, Kazuyuki Ohbo, Haruhiko Koseki

Research output: Contribution to journalArticlepeer-review

Abstract

Heterochromatin-related epigenetic mechanisms, such as DNA methylation, facilitate pairing of homologous chromosomes during the meiotic prophase of mammalian spermatogenesis. In prospermatogonia, de novo DNA methylation plays a key role in completing meiotic prophase and initiating meiotic division. However, the role of maintenance DNA methylation in the regulation of meiosis, especially in the adult, is not well understood. Here, we reveal that NP95 (also known as UHRF1) and DNMT1 - two essential proteins for maintenance DNA methylation - are coexpressed in spermatogonia and are necessary for meiosis in male germ cells. We find that Np95- or Dnmt1-deficient spermatocytes exhibit spermatogenic defects characterized by synaptic failure during meiotic prophase. In addition, assembly of pericentric heterochromatin clusters in early meiotic prophase, a phenomenon that is required for subsequent pairing of homologous chromosomes, is disrupted in both mutants. Based on these observations, we propose that DNA methylation, established in pre-meiotic spermatogonia, regulates synapsis of homologous chromosomes and, in turn, quality control of male germ cells. Maintenance DNAmethylation, therefore, plays a role in ensuring faithful transmission of both genetic and epigenetic information to offspring.

Original languageEnglish
Article numberdev194605
JournalDevelopment (Cambridge)
Volume148
Issue number10
DOIs
Publication statusPublished - May 2021

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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