Vertebrate nucleoplasmin and NASP: egg histone storage proteins with multiple chaperone activities

Abstract

Recent reviews have focused on the structure and function of histone chaperones involved in different aspects of somatic cell chromatin metabolism. One of the most dramatic chromatin remodeling processes takes place immediately after fertilization and is mediated by egg histone storage chaperones. These include members of the nucleoplasmin (NPM2/NPM3), which are preferentially associated with histones H2A-H2B in the egg and the nuclear autoantigenic sperm protein (NASP) families. Interestingly, in addition to binding and providing storage to H3/H4 in the egg and in somatic cells, NASP has been shown to be a unique genuine chaperone for histone H1. This review revolves around the structural and functional roles of these two families of chaperones whose activity is modulated by their own post-translational modifications (PTMs), particularly phosphorylation. Beyond their important role in the remodeling of paternal chromatin in the early stages of embryogenesis, NPM and NASP members can interact with a plethora of proteins in addition to histones in somatic cells and play a critical role in processes of functional cell alteration, such as in cancer. Despite their common presence in the egg, these two histone chaperones appear to be evolutionarily unrelated. In contrast to members of the NPM family, which share a common monophyletic evolutionary origin, the different types of NASP appear to have evolved recurrently within different taxa.

The intrinsically disordered distal face of nucleoplasmin recognizes distinct oligomerization states of histones

“…NPM1, a member of the NP/nucleophosmin family present in oocytes, embryonary and adult cells that has been involved in ribosome biogenesis and association with pre-ribosomal RNP particles DNA (23,78), also forms complexes with H3-H4 and histone octamers in vitro (13,45,78). Although this shared ability could suggest that these assemblies might display a specific biological function in the nucleolus of normal cells, their existence in vivo remains to be proved.…”

“…The NP distal face seems to be a versatile partner, as it also binds linker histones H1 and H5 and linker-related sperm-specific binding proteins (SSBP) (22). Thus, NP as other histone chaperones (5,23–25) can bind several histone ligands, an ability that is probably related to the distinct processes they are involved in. In this context, NP has been proposed to play a role in histone storage in the oocyte preventing their aggregation or inefficient interaction with other partners, decondensation of sperm chromatin after fertilization by removing DNA-bound SSBP, replication licensing and nucleosome assembly in early embryonic cells (7,26).…”

Nucleolin and nucleophosmin: nucleolar proteins with multiple functions in DNA repair

“…Each of these three proteins is conserved throughout vertebrates, while more evolutionarily distant members of the family may be found in invertebrates and in lower eukaryotes (Edlich-Muth et al 2015;Frehlick et al 2007;Gudavicius et al 2014), and all three possess the ability to bind histones, regulate their assembly into nucleosomes and promote their loading onto and/or eviction from DNA, identifying them as true histone chaperones (Frehlick et al 2007;Finn et al 2012). While NPM2 and NPM3 appear in vivo to function exclusively as histone chaperones during both somatic cell growth and, in particular, gametogenesis and fertilization (Finn et al 2012;Okuwaki et al 2012), NPM1 has gained numerous additional functions during evolution and acts in numerous independent cellular pathways. The NPM1 gene encodes two protein isoforms, termed B23.1 (294 amino acids) and B23.2 (259 amino acids), which differ by splicing at their C-termini (Colombo et al 2011).…”

“…The oligomerization of NPM1 is essential for at least some of its functions in vivo, likely through allowing simultaneous and closely juxtaposed binding of multiple targets or of multi-subunit complexes (Thyagarajan et al 1998;Xia et al 2013). Interestingly, NPM3 has not been reported to form homopentameric rings and is unable to act as a histone chaperone in its own right; instead, it assembles into hetero-oligomers with NPM1, in doing so promoting the histone chaperone activity of NPM1 while repressing its RNA-binding and ribosome biogenesis activities (Finn et al 2012;Huang et al 2005;Okuwaki et al 2012). D r a f t 8 Consistent with its identification as a nucleolar phosphoprotein, NPM1 undergoes extensive posttranslational modifications including phosphorylation, ubiquitination and SUMOylation, arginine methylation, lysine acetylation and others (Colombo et al 2011), demonstrating it to be a highly regulated protein in vivo.…”

Shaping Chromatin in the Nucleus: The Bricks and the Architects

“…For example, in Xenopus, unusually high levels of Npm2 (nucleoplasmin 2), the first described histone chaperone (Laskey et al 1978), are present in the oocyte and during early embryogenesis (Burglin et al 1987;Litvin and King 1988). This elevated dosage of the architect Npm2 ensures storage of soluble histones H2A-H2B contributing to chromatin assembly after fertilization during the rapid cell divisions in early development (Finn et al 2012). In adult tissues, concentration of Npm2 decreases in parallel with the lower rate of cell division.…”