A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility

Fernández-Rivero, Noelia; Franco, Aitor; Velázquez‐Campoy, Adrián; Alonso, Edurne; Muga, Arturo; Prado, Adelina

doi:10.1038/srep32114

Cited by 17 publications

(24 citation statements)

References 66 publications

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“…The stoichiometry of this complex was 1:1 tail:H3/H4 dimer (Supplementary Fig. 7c ), and is also consistent with the recently reported binding affinity and stoichiometry of Npm to H3/H4 27 .…”

Section: Resultssupporting

confidence: 91%

Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release

et al. 2017

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Nucleoplasmin (Npm) is a highly conserved histone chaperone responsible for the maternal storage and zygotic release of histones H2A/H2B. Npm contains a pentameric N-terminal core domain and an intrinsically disordered C-terminal tail domain. Though intrinsically disordered regions are common among histone chaperones, their roles in histone binding and chaperoning remain unclear. Using an NMR-based approach, here we demonstrate that the Xenopus laevis Npm tail domain controls the binding of histones at its largest acidic stretch (A2) via direct competition with both the C-terminal basic stretch and basic nuclear localization signal. NMR and small-angle X-ray scattering (SAXS) structural analyses allowed us to construct models of both the tail domain and the pentameric complex. Functional analyses demonstrate that these competitive intramolecular interactions negatively regulate Npm histone chaperone activity in vitro. Together these data establish a potentially generalizable mechanism of histone chaperone regulation via dynamic and specific intramolecular shielding of histone interaction sites.

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Section: Resultssupporting

confidence: 91%

Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release

et al. 2017

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“…As previously demonstrated, npm2b functions as a histone chaperone to decondense sperm DNA as well as reorganize chromatin, thus, it has also been suggested to contribute to ZGA as well. [ 5 , 11 , 34 , 39 ] Npm2b is thought to be activated by various post-translational modifications and homo-pentamerisation [ 40 ], and subsequently interacts with chromatin by exchanging sperm-specific basic proteins with histones via its core domain and acidic tracts A1, A2 and A3 [ 32 , 36 , 38 , 41 – 44 ]. We found that most of the investigated Npm2a proteins possess acidic tract A1 while some have a shortened A2, in contrast to Npm2b proteins which have a long A2 and mostly lack A1.…”

Section: Resultsmentioning

confidence: 99%

Double maternal-effect: duplicated nucleoplasmin 2 genes, npm2a and npm2b, with essential but distinct functions are shared by fish and tetrapods

et al. 2018

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BackgroundNucleoplasmin 2 (npm2) is an essential maternal-effect gene that mediates early embryonic events through its function as a histone chaperone that remodels chromatin. Recently, two npm2 (npm2a and npm2b) genes have been annotated in zebrafish. Thus, we examined the evolution of npm2a and npm2b in a variety of vertebrates, their potential phylogenetic relationships, and their biological functions using knockout models via the CRISPR/cas9 system.ResultsWe demonstrated that the two npm2 duplicates exist in a wide range of vertebrates, including sharks, ray-finned fish, amphibians, and sauropsids, while npm2a was lost in coelacanth and mammals, as well as some specific teleost lineages. Using phylogeny and synteny analyses, we traced their origins to the early stages of vertebrate evolution. Our findings suggested that npm2a and npm2b resulted from an ancient local gene duplication, and their functions diverged although key protein domains were conserved. We then investigated their functions by examining their tissue distribution in a wide variety of species and found that they shared ovarian-specific expression, a key feature of maternal-effect genes. We also demonstrated that both npm2a and npm2b are maternally-inherited transcripts in vertebrates, and that they play essential, but distinct, roles in early embryogenesis using zebrafish knockout models. Both npm2a and npm2b function early during oogenesis and may play a role in cortical granule function that impact egg activation and fertilization, while npm2b is also involved in early embryogenesis.ConclusionThese novel findings will broaden our knowledge on the evolutionary history of maternal-effect genes and underlying mechanisms that contribute to vertebrate reproductive success. In addition, our results demonstrate the existence of a newly described maternal-effect gene, npm2a, that contributes to egg competence, an area that still requires further comprehension.Electronic supplementary materialThe online version of this article (10.1186/s12862-018-1281-3) contains supplementary material, which is available to authorized users.

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“…NPM-fold histone chaperones also oligomerize, forming pentameric rings 61,62 (FIG. 3E) that are capable of binding multiple copies of various histone subtypes (TABLE 1) and promote tetrasome assembly 63,64 .…”

Section: Mechanistic Insights Into Chaperoning Histonesmentioning

confidence: 99%

Histone chaperone networks shaping chromatin function

Hammond

Strømme

Huang

et al. 2017

Nat Rev Mol Cell Biol

435

419

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The association of histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified histones evicted from chromatin.

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A Quantitative Characterization of Nucleoplasmin/Histone Complexes Reveals Chaperone Versatility

Cited by 17 publications

References 66 publications

Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release

Dynamic intramolecular regulation of the histone chaperone nucleoplasmin controls histone binding and release

Double maternal-effect: duplicated nucleoplasmin 2 genes, npm2a and npm2b, with essential but distinct functions are shared by fish and tetrapods

Histone chaperone networks shaping chromatin function

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