sNASP, a Histone H1-Specific Eukaryotic Chaperone Dimer that Facilitates Chromatin Assembly

Abstract

NASP has been described as a histone H1 chaperone in mammals. However, the molecular mechanisms involved have not yet been characterized. Here, we show that this protein is not only present in mammals but is widely distributed throughout eukaryotes both in its somatic and testicular forms. The secondary structure of the human somatic version consists mainly of clusters of alpha-helices and exists as a homodimer in solution. The protein binds nonspecifically to core histone H2A-H2B dimers and H3-H4 tetramers but only forms specific complexes with histone H1. The formation of the NASP-H1 complexes is mediated by the N- and C-terminal domains of histone H1 and does not involve the winged helix domain that is characteristic of linker histones. In vitro chromatin reconstitution experiments show that this protein facilitates the incorporation of linker histones onto nucleosome arrays and hence is a bona fide linker histone chaperone.

The Presence of HIV-1 Tat Protein Second Exon Delays Fas Protein-mediated Apoptosis in CD4+ T Lymphocytes

“…The low caspase-3 activity detected in Jurkat-Tat101 would contribute to MCM3 stability and therefore to the maintenance of the MCM complex, avoiding apoptosis. Other factors related to cell cycle progression, cytokinesis, and cell proliferation were also overexpressed in Jurkat-Tat101, such as NUDC, NASP, and PCNA (102)(103)(104)(105). The overexpression of somatic NASP has been related to changes in NF-B activity (106), which is known to be enhanced by Tat (23,70).…”

Chaperone-mediated chromatin assembly and transcriptional regulation in Xenopus laevis

“…Nucleoplasmin, when heavily phosphorylated and otherwise modified in the egg, decondenses sperm chromatin (Philpott et al , 1991) yet binds and sequesters core histones (Onikubo et al , 2015). NASP participates in H3-H4 dimer assembly in the cytoplasm (Campos et al , 2010), stores H3-H4 in the egg (Finn et al , 2012), and also directly transfers linker histones into the nucleus (Finn et al , 2008). Asf1 is a histone chaperone responsible for H3-H4 import into nucleus, but Asf1 has also been implicated in the disassembly of nucleosomes during DNA replication and during transcription (English et al , 2006).…”

Chromatin and DNA Replication

“…Newly synthesized histone H3 -H4 dimers are delivered to the replication fork by ASF1 for deposition by CAF-1 (4) or, in the case of histone H2A-H2B dimers, by NAP1 (5). and histone dynamics; for example, nuclear autoantigenic sperm protein (NASP), initially reported as a histone H1 linker chaperone (Finn et al 2008), was later found to function as an H3 -H4 chaperone (Osakabe et al 2010) as part of a multichaperone complex Groth et al 2005). Recent work indicates that NASP may act to fine-tune soluble H3 levels by counteracting degradation involving the chaperone-mediated autophagy pathway (Cook et al 2011).…”