Alternative titles; symbols
HGNC Approved Gene Symbol: NAP1L1
Cytogenetic location: 12q21.2 Genomic coordinates (GRCh38): 12:76,036,585-76,084,685 (from NCBI)
From a human thymus cDNA library, Simon et al. (1994) isolated a cDNA encoding a protein with 54% amino acid similarity to yeast nucleosome assembly protein I (NAPI). The deduced amino acid sequence of the identified protein, designated NRP (for 'NAP-related protein'), has a potential 7-residue nuclear localization motif, 3 clusters of highly acidic residues, and other structural features found in various proteins implicated in chromatin formation. NRP transcript was detected in all human tissues and cell lines studied, but levels were somewhat increased in rapidly proliferating cells. This and other observations suggested to the authors that the NRP gene product participates in DNA replication and therefore plays an important role in the process of cell proliferation.
Hajkova et al. (2008) studied epigenetic changes in primordial germ cells (PGCs) in the mouse lineage. They showed that the chromatin changes occur in 2 steps. The first changes in nascent PGCs at embryonic day 8.5 establish a distinctive chromatin signature that is reminiscent of pluripotency. Next, when PGCs are residing in the gonads, major changes occur in nuclear architecture accompanied by an extensive erasure of several histone modifications and exchange of histone variants. Furthermore, the histone chaperones HIRA (600237) and NAP1, which are implicated in histone exchange, accumulate in PGC nuclei undergoing reprogramming. Hajkova et al. (2008) therefore suggested that the mechanism of histone replacement is critical for these chromatin rearrangements to occur. The marked chromatin changes are intimately linked with genomewide DNA demethylation. On the basis of the timing of the observed events, Hajkova et al. (2008) proposed that if DNA demethylation entails a DNA repair-based mechanism, the evident histone replacement would represent a repair-induced response event rather than being a prerequisite.
NAP1 and NAP2 (NAP1L4; 601651) facilitate nucleosome assembly by first depositing preformed tetramers made up of 2 molecules each of histones H3 (see 602810) and H4 (see 602822) onto DNA prior to the addition of tetramers made up of 2 molecules each of histones H2A (see 142720) and H2B (see 609904). Using recombinant human proteins in an in vitro nucleosome formation assay, Tachiwana et al. (2008) confirmed that both NAP1 and NAP2 promoted formation of nucleosomes containing the conventional histones H2A, H2B, H3.1 (see 602810), and H4. NAP1 could also promote nucleosome assembly with the H3 variants H3.2 (HIST2H3C; 142780), H3.3 (see 601128), and CENPA (117139), but not the testis-specific H3 variant H3T (HIST3H3; 602820). In contrast, NAP2 promoted nucleosome assembly with H3T, bound H3T/H4 tetramers efficiently, and was released from H3T/H4 tetramers in the presence of DNA. Mutation analysis revealed that a change of ala111, which is conserved among H3.1, H3.2, and H3.3, to val in H3T was responsible for the differential binding of these H3 variants to NAP1.
Park and Luger (2006) resolved the crystal structure of yeast Nap1 to 3.0-angstrom resolution. They determined that a long alpha helix mediates homodimerization, and a domain containing both alpha helices and beta sheets mediates protein-protein interactions. A nuclear export sequence embedded in the dimerization helix is almost completely masked by an accessory domain containing several putative phosphorylation sites. Human NAP1 shares conserved motifs and a similar protein structure with yeast Nap1.
Stumpf (2024) mapped the NAP1L1 gene to chromosome 12q21.2 based on an alignment of the NAP1L1 sequence (GenBank AK297500) with the genomic sequence (GRCh38).
Hajkova, P., Ancelin, K., Waldmann, T., Lacoste, N., Lange, U. C., Cesari, F., Lee, C., Almouzni, G., Schneider, R., Surani, M. A. Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature 452: 877-881, 2008. [PubMed: 18354397] [Full Text: https://doi.org/10.1038/nature06714]
Park, Y.-J., Luger, K. The structure of nucleosome assembly protein 1. Proc. Nat. Acad. Sci. 103: 1248-1253, 2006. [PubMed: 16432217] [Full Text: https://doi.org/10.1073/pnas.0508002103]
Simon, H.-U., Mills, G. B., Kozlowski, M., Hogg, D., Branch, D., Ishimi, Y., Siminovitch, K. A. Molecular characterization of hNRP, a cDNA encoding a human nucleosome-assembly-protein-I-related gene product involved in the induction of cell proliferation. Biochem. J. 297: 389-397, 1994. [PubMed: 8297347] [Full Text: https://doi.org/10.1042/bj2970389]
Stumpf, A. M. Personal Communication. Baltimore, Md. 03/15/2024.
Tachiwana, H., Osakabe, A., Kimura, H., Kurumizaka, H. Nucleosome formation with the testis-specific histone H3 variant, H3t, by human nucleosome assembly proteins in vitro. Nucleic Acids Res. 36: 2208-2218, 2008. [PubMed: 18281699] [Full Text: https://doi.org/10.1093/nar/gkn060]