2024
Cell Reports

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

Authors:

Zexiong Lin, Dongliang Li, Jiahuan Zheng, Louise T. Chow, Hengbin Wang, Kui Liu

Keywords:

MAPS, phase separation, meiotic prophase I, sex body formation, male infertility

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.