Developmentally regulated post-translational modification of nucleoplasmin controls histone sequestration and deposition

Takashi Onikubo, Joshua J. Nicklay, Li Xing, Christopher Warren, Brandon Anson, Wei Lin Wang, Emmanuel S. Burgos, Sophie E. Ruff, Jeffrey Shabanowitz, R. Holland Cheng, Donald F. Hunt, David Shechter

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1735-1748
Number of pages14
JournalCell Reports
Volume10
Issue number10
DOIs
StatePublished - Mar 17 2015

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Nucleoplasmins
Post Translational Protein Processing
Histones
Oocytes
Ovum
Tail
Histone Chaperones
Phosphorylation
Methylation
Chromatin Assembly and Disassembly
Nucleosomes
Xenopus laevis
Electron microscopy
Chromatin
Embryonic Development
Mass spectrometry
Arginine
Conformations
Vertebrates
Assays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Developmentally regulated post-translational modification of nucleoplasmin controls histone sequestration and deposition. / Onikubo, Takashi; Nicklay, Joshua J.; Xing, Li; Warren, Christopher; Anson, Brandon; Wang, Wei Lin; Burgos, Emmanuel S.; Ruff, Sophie E.; Shabanowitz, Jeffrey; Cheng, R. Holland; Hunt, Donald F.; Shechter, David.

In: Cell Reports, Vol. 10, No. 10, 17.03.2015, p. 1735-1748.

Research output: Contribution to journalArticle

Onikubo, T, Nicklay, JJ, Xing, L, Warren, C, Anson, B, Wang, WL, Burgos, ES, Ruff, SE, Shabanowitz, J, Cheng, RH, Hunt, DF & Shechter, D 2015, 'Developmentally regulated post-translational modification of nucleoplasmin controls histone sequestration and deposition', Cell Reports, vol. 10, no. 10, pp. 1735-1748. https://doi.org/10.1016/j.celrep.2015.02.038
Onikubo, Takashi ; Nicklay, Joshua J. ; Xing, Li ; Warren, Christopher ; Anson, Brandon ; Wang, Wei Lin ; Burgos, Emmanuel S. ; Ruff, Sophie E. ; Shabanowitz, Jeffrey ; Cheng, R. Holland ; Hunt, Donald F. ; Shechter, David. / Developmentally regulated post-translational modification of nucleoplasmin controls histone sequestration and deposition. In: Cell Reports. 2015 ; Vol. 10, No. 10. pp. 1735-1748.
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