Alternative titles; symbols
HGNC Approved Gene Symbol: NAP1L4
Cytogenetic location: 11p15.4 Genomic coordinates (GRCh38): 11:2,944,437-2,992,329 (from NCBI)
Hu et al. (1996) used a positional cloning approach to isolate a gene which is located 100 kb centromeric to the proximal Beckwith-Wiedemann breakpoint cluster region (BWS; 130650) on chromosome 11p15. This gene is homologous to the yeast nucleosome assembly protein NAP1 (164060). The authors designated the new gene NAP2. They demonstrated that this gene shows biallelic expression in all tissues tested and that it therefore diverges in its expression from IGF2 (147470), H19 (103280), and p57(KIP2) (600856), which also map to 11p15.5 in the vicinity of the BWS gene. The NAP2 gene encodes a highly acidic protein of 375 amino acids.
Rodriguez et al. (1997) reported that the NAP1L4 gene consists of 14 exons and spans approximately 30.5 kb. A 1,200-bp 3-prime untranslated region was present.
Hu et al. (1996) mapped the NAP1L4 gene to chromosome 11p15.5.
Histones are thought to play a key role in regulating gene expression at the level of DNA packaging. The deduced amino acid sequence of NAP2 indicates that it is a protein with a potential nuclear localization motif and 2 clusters of highly acidic residues. By functional analysis of recombinant NAP2 protein purified from Escherichia coli, Rodriguez et al. (1997) found that this protein can interact with both core and linker histones (see 142709). They demonstrated that recombinant NAP2 can transfer histones onto naked DNA templates. Subcellular localization studies of NAP2 indicated that it can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone.
NAP1 and NAP2 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.
NAP1L4 maps to a region implicated in Wilms tumor etiology (see 194071). Rodriguez et al. (1997) analyzed the gene encoding NAP2 for mutations and found no evidence of nonsense, frameshift, or deletion mutations. Their findings, coupled with tumor suppression assays in Wilms tumor cells, did not support a role for NAP2 in the etiology of that neoplasm.
Hu, R.-J., Lee, M. P., Johnson, L. A., Feinberg, A. P. A novel human homologue of yeast nucleosome assembly protein, 65 kb centromeric to the p57(KIP2) gene, is biallelically expressed in fetal and adult tissues. Hum. Molec. Genet. 5: 1743-1748, 1996. [PubMed: 8923002] [Full Text: https://doi.org/10.1093/hmg/5.11.1743]
Rodriguez, P., Munroe, D., Prawitt, D., Chu, L. L., Bric, E., Kim, J., Reid, L. H., Davies, C., Nakagama, H., Loebbert, R., Winterpacht, A., Petruzzi, M.-J., Higgins, M. J., Nowak, N., Evans, G., Shows, T., Weissman, B. E., Zabel, B., Housman, D. E., Pelletier, J. Functional characterization of human nucleosome assembly protein-2 (NAP1L4) suggests a role as a histone chaperone. Genomics 44: 253-265, 1997. [PubMed: 9325046] [Full Text: https://doi.org/10.1006/geno.1997.4868]
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]