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The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.

ABSTRACT: Histones are essential for chromatin packaging, and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones, but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila homolog of NASP, is a H3-H4-specific chaperone in the early embryo. We demonstrate that, while a NASP null mutant is viable in Drosophila, NASP is a maternal effect gene. Embryos laid by NASP mutant mothers have a reduced rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo.

SUBMITTER: Tirgar R

PROVIDER: S-EPMC10058107 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.

Tirgar Reyhaneh R Davies Jonathan P JP Plate Lars L Nordman Jared T JT

PLoS genetics 20230317 3

Histones are essential for chromatin packaging, and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones, but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila homolog of NASP, is a H3-H4-specific chaperone in th ...[more]

PMID: 36930688

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Project description:BackgroundNASP is an essential protein in mammals that functions in histone transport pathways and maintenance of a soluble reservoir of histones H3/H4. NASP has been studied exclusively in Opisthokonta lineages where some functional diversity has been reported. In humans, growing evidence implicates NASP miss-regulation in the development of a variety of cancers. Although a comprehensive phylogenetic analysis is lacking, NASP-family proteins that possess four TPR motifs are thought to be widely distributed across eukaryotes.ResultsWe characterize the molecular evolution of NASP by systematically identifying putative NASP orthologs across diverse eukaryotic lineages ranging from excavata to those of the crown group. We detect extensive silent divergence at the nucleotide level suggesting the presence of strong purifying selection acting at the protein level. We also observe a selection bias for high frequencies of acidic residues which we hypothesize is a consequence of their critical function(s), further indicating the role of functional constraints operating on NASP evolution. Our data indicate that TPR1 and TPR4 constitute the most rapidly evolving functional units of NASP and may account for the functional diversity observed among well characterized family members. We also show that NASP paralogs in ray-finned fish have different genomic environments with clear differences in their GC content and have undergone significant changes at the protein level suggesting functional diversification.ConclusionWe draw four main conclusions from this study. First, wide distribution of NASP throughout eukaryotes suggests that it was likely present in the last eukaryotic common ancestor (LECA) possibly as an important innovation in the transport of H3/H4. Second, strong purifying selection operating at the protein level has influenced the nucleotide composition of NASP genes. Further, we show that selection has acted to maintain a high frequency of functionally relevant acidic amino acids in the region that interrupts TPR2. Third, functional diversity reported among several well characterized NASP family members can be explained in terms of quickly evolving TPR1 and TPR4 motifs. Fourth, NASP fish specific paralogs have significantly diverged at the protein level with NASP2 acquiring a NNR domain.

Dataset Information

The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.

Publications

The histone chaperone NASP maintains H3-H4 reservoirs in the early Drosophila embryo.

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