PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

Chang Rok Kim, Taichi Noda, Hyunkyung Kim, Gibeom Kim, Seongwan Park, Yongwoo Na, Seiya Oura, Keisuke Shimada, Injin Bang, Jun Yeong Ahn, Yong Ryoul Kim, Se Kyu Oh, Hee Jung Choi, Jong Seo Kim, Inkyung Jung, Ho Lee, Yuki Okada, Masahito Ikawa, Sung Hee Baek

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Spermatogenesis is a complex process of sperm generation, including mitosis, meiosis, and spermiogenesis. During spermiogenesis, histones in post-meiotic spermatids are removed from chromatin and replaced by protamines. Although histone-to-protamine exchange is important for sperm nuclear condensation, the underlying regulatory mechanism is still poorly understood. Here, we identify PHD finger protein 7 (PHF7) as an E3 ubiquitin ligase for histone H3K14 in post-meiotic spermatids. Generation of Phf7-deficient mice and Phf7 C160A knockin mice with impaired E3 ubiquitin ligase activity reveals defects in histone-to-protamine exchange caused by dysregulation of histone removal factor Bromodomain, testis-specific (BRDT) in early condensing spermatids. Surprisingly, E3 ubiquitin ligase activity of PHF7 on histone ubiquitination leads to stabilization of BRDT by attenuating ubiquitination of BRDT. Collectively, our findings identify PHF7 as a critical factor for sperm chromatin condensation and contribute to mechanistic understanding of fundamental phenomenon of histone-to-protamine exchange and potential for drug development for the male reproduction system. Histone-to-protamine exchange is essential for functional sperm. Kim et al. demonstrate that PHF7 is an E3 ubiquitin ligase for histone H3, and that PHF7-mediated histone ubiquitination regulates BRDT stability during histone removal. Mice with impaired Phf7 show dysfunctional sperm caused by defects in histone ubiquitination and histone-to-protamine exchange.

Original languageEnglish
Article number107950
JournalCell Reports
Volume32
Issue number4
DOIs
Publication statusPublished - 2020 Jul 28

Keywords

  • BRDT
  • H3K14ub
  • H4 hyperacetylation
  • histone removal
  • histone-to-protamine exchange
  • PHF7
  • spermiogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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