title: Developmentally Regulated Post-translational Modification of Nucleoplasmin Controls Histone Sequestration and Deposition.
abstract: Nucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Onikubo
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA 22901, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Nicklay
authors.affiliation: Department of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Warren
authors.affiliation: Department of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Anson
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Wei-Lin
authors.initials: WL
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Burgos
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA.
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Ruff
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, VA 22901, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.affiliation: Department of Molecular and Cellular Biology, University of California-Davis, Davis, CA 95616, USA.
authors.forename: R Holland
authors.initials: RH
authors.lastname: Cheng
authors.affiliation: Departments of Chemistry and Pathology, University of Virginia, Charlottesville, VA 22904, USA. Electronic address: dfh@virginia.edu.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA. Electronic address: david.shechter@einstein.yu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Shechter