The male pachynema-specific protein MAPS drives phase separation in vitro and regulates sex body formation and chromatin behaviors in vivo

Zexiong Lin; Dongliang Li; Jiahuan Zheng; Chencheng Yao; Dongteng Liu; Hao Zhang; Haiwei Feng; Chunxu Chen; Peng Li; Yuxiang Zhang; Binjie Jiang; Zhe Hu; Yu Zhao; Fu Shi; Dandan Cao; Kenny A Rodriguez-Wallberg; Zheng Li; William S B Yeung; Louise T Chow; Hengbin Wang; Kui Liu

doi:10.1016/j.celrep.2023.113651

The male pachynema-specific protein MAPS drives phase separation in vitro and regulates sex body formation and chromatin behaviors in vivo

Cell Rep. 2024 Jan 23;43(1):113651. doi: 10.1016/j.celrep.2023.113651. Epub 2024 Jan 3.

Authors

Zexiong Lin¹, Dongliang Li¹, Jiahuan Zheng¹, Chencheng Yao², Dongteng Liu¹, Hao Zhang³, Haiwei Feng¹, Chunxu Chen⁴, Peng Li², Yuxiang Zhang², Binjie Jiang¹, Zhe Hu¹, Yu Zhao¹, Fu Shi¹, Dandan Cao¹, Kenny A Rodriguez-Wallberg⁵, Zheng Li², William S B Yeung¹, Louise T Chow⁶, Hengbin Wang⁷, Kui Liu⁸

Affiliations

¹ Department of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine; Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, The University of Hong Kong, Hong Kong, China.
² Department of Andrology, Center for Men's Health, Department of ART, Institute of Urology, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
³ Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.
⁴ Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Massey Cancer Institute, Virginia Commonwealth University, Richmond, VA, USA.
⁵ Department of Oncology-Pathology, The Karolinska Institute, 14186 Stockholm, Sweden.
⁶ Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: [email protected].
⁷ Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Massey Cancer Institute, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: [email protected].
⁸ Department of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine; Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, The University of Hong Kong, Hong Kong, China. Electronic address: [email protected].

PMID: 38175751
DOI: 10.1016/j.celrep.2023.113651

Abstract

Dynamic chromosome remodeling and nuclear compartmentalization take place during mammalian meiotic prophase I. We report here that the crucial roles of male pachynema-specific protein (MAPS) in pachynema progression might be mediated by its liquid-liquid phase separation in vitro and in cellulo. MAPS forms distinguishable liquid phases, and deletion or mutations of its N-terminal amino acids (aa) 2-9 disrupt its secondary structure and charge properties, impeding phase separation. Maps^-/- pachytene spermatocytes exhibit defects in nucleus compartmentalization, including defects in forming sex bodies, altered nucleosome composition, and disordered chromatin accessibility. Maps^Δ2-9/Δ2-9 male mice expressing MAPS protein lacking aa 2-9 phenocopy Maps^-/- mice. Moreover, a frameshift mutation in C3orf62, the human counterpart of Maps, is correlated with nonobstructive azoospermia in a patient exhibiting pachynema arrest in spermatocyte development. Hence, the phase separation property of MAPS seems essential for pachynema progression in mouse and human spermatocytes.

Keywords: CP: Cell biology; CP: Molecular biology; MAPS; male infertility; meiotic prophase I; phase separation; sex body formation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromatin* / metabolism
Humans
Male
Mammals / genetics
Meiosis*
Meiotic Prophase I
Mice
Pachytene Stage
Phase Separation
Spermatocytes / metabolism

Substances

Chromatin