title: Function of homo- and hetero-oligomers of human nucleoplasmin/nucleophosmin family proteins NPM1, NPM2 and NPM3 during sperm chromatin remodeling.
abstract: Sperm chromatin remodeling after oocyte entry is the essential step that initiates embryogenesis. This reaction involves the removal of sperm-specific basic proteins and chromatin assembly with histones. In mammals, three nucleoplasmin/nucleophosmin (NPM) family proteins-NPM1, NPM2 and NPM3-expressed in oocytes are presumed to cooperatively regulate sperm chromatin remodeling. We characterized the sperm chromatin decondensation and nucleosome assembly activities of three human NPM proteins. NPM1 and NPM2 mediated nucleosome assembly independently of other NPM proteins, whereas the function of NPM3 was largely dependent on formation of a complex with NPM1. Maximal sperm chromatin remodeling activity of NPM2 required the inhibition of its non-specific nucleic acid-binding activity by phosphorylation. Furthermore, the oligomer formation with NPM1 elicited NPM3 nucleosome assembly and sperm chromatin decondensation activity. NPM3 also suppressed the RNA-binding activity of NPM1, which enhanced the nucleoplasm-nucleolus shuttling of NPM1 in somatic cell nuclei. Our results proposed a novel mechanism whereby three NPM proteins cooperatively regulate chromatin disassembly and assembly in the early embryo and in somatic cells.
authors.affiliation: Faculty of Medicine and Graduate School of Comprehensive Human Sciences, Initiative for Promotion of Young Scientists' Independent Research, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan. mokuwaki@md.tsukuba.ac.jp
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okuwaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Sumi
authors.forename: Miharu
authors.initials: M
authors.lastname: Hisaoka
authors.forename: Ai
authors.initials: A
authors.lastname: Saotome-Nakamura
authors.forename: Satoko
authors.initials: S
authors.lastname: Akashi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D006367:HeLa Cells; D056488:Histone Chaperones / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D056489:Nucleoplasmins / Q000378:metabolism*; D010766:Phosphorylation; D055503:Protein Multimerization; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D056488:Histone Chaperones; C000716967:NPM1 protein, human; C533550:NPM2 protein, human; C533551:NPM3 protein, human; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D056489:Nucleoplasmins; D000090243:Nucleophosmin