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

Highly dynamic chromosome remodeling and extensive nuclear compartmentalization occur during mammalian meiotic prophase I. We report here that mouse spermatocytes lacking MAPS, the male pachynema-specific protein, exhibit multiple pachytene defects, including disordered chromatin accessibility, interrupted nucleosome composition, and globally altered transcription, accompanied by disturbed nucleus phase formation. Adult Maps−/− pachytene spermatocytes lack sex body formation and exhibit improper autosomal chromatin condensation, which can be attributed to the feature of MAPS to mediate phase separation through its unique intrinsically disordered regions (IDRs), amino acids 2-9. MAPS protein with deletion of IDR failed to form a distinguishable phase in vitro and in cultured cells, and remarkably, MAPS IDR-deleted male mice suffer from pachytene arrest and sterility, with a typical absence of sex body and less condensed autosomal chromosomes, similar to Maps−/− mice. Thus, the nucleus phase separation mediated by MAPS may be essential for male pachynema progression in mice. To check the MSCI status of pachytene cells after MAPS protein deletion, pachytene cells from WT, MAPS-/- and MAPSEE;MAPS-/- groups (postnatal date ~80 day) were purified by STA-PUT method. Three mice with identical genotypes for each group were used for pachytene cell purification. RNA-seq were conducted with two independent experiments.