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
Affiliations
Chang Rok Kim
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Taichi Noda
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Hyunkyung Kim
Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul 02841, South Korea
Gibeom Kim
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Seongwan Park
Department of Biological Sciences, Korea Advanced Institute of Science & Technology, Daejeon 34141, South Korea
Yongwoo Na
Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea; Center for RNA Research, Institute for Basic Science, Seoul 08826, South Korea
Seiya Oura
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Keisuke Shimada
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
Injin Bang
Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Jun-Yeong Ahn
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Yong Ryoul Kim
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Se Kyu Oh
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Hee-Jung Choi
Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea
Jong-Seo Kim
Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea; Center for RNA Research, Institute for Basic Science, Seoul 08826, South Korea
Inkyung Jung
Department of Biological Sciences, Korea Advanced Institute of Science & Technology, Daejeon 34141, South Korea
Ho Lee
Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center, Goyang 10408, South Korea
Yuki Okada
Laboratory of Pathology and Development, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo 113-0032, Japan
Masahito Ikawa
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Corresponding author
Sung Hee Baek
Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul 08826, South Korea; Department of Biological Sciences, Seoul National University, Seoul 08826, South Korea; Corresponding author
Summary: 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.
