Alternative titles; symbols
HGNC Approved Gene Symbol: NAP1L2
Cytogenetic location: Xq13.2 Genomic coordinates (GRCh38): X:73,212,299-73,214,851 (from NCBI)
As part of studies of the X-inactivation center on the X chromosome in mice, Rougeulle and Avner (1996) cloned and characterized a gene, which they called Bpx. Bpx, which is specifically expressed in the brain, shows strong homology to genes encoding nucleosome assembly proteins (e.g., 164060) and is normally X-inactivated in mice. (BPX is presumably for 'brain protein on X.') Rougeulle and Avner (1996) also isolated human BPX.
By RNA in situ hybridization on sections of mouse embryos and adult mouse brain, Rogner et al. (2000) detected the first expression of Nap1l2 at embryonic day 10.5, which correlates with the onset of neuronal differentiation in the central and peripheral nervous systems. Nap1l2 was mainly expressed in neurons, and most strongly in postmitotic neurons.
Rougeulle and Avner (1996) found evidence that BPX, like its murine homolog, is an intronless gene.
Rougeulle and Avner (1996) located the mouse Bpx gene distal to the Xist locus (314670). They mapped the human BPX gene centromeric to XIST. Rougeulle and Avner (1996) concluded that the Xq13 region, in which gene orientation is apparently globally conserved between man and mouse, must therefore contain an inversion of at least 600 kb spanning the XIST sequence and including the CDX4 (300025) and BPX genes.
Rogner et al. (2000) inactivated the Nap1l2 gene in mice by gene targeting, leading to embryonic lethality from midgestation onwards. Surviving mutant chimeric embryos showed extensive surface ectoderm defects as well as the presence of open neural tubes and exposed brains similar to those observed in human spina bifida and anencephaly. These defects correlated with an overproduction of neuronal precursor cells. Protein expression studies showed that the Nap1l2 protein binds to condensing chromatin during S phase and in apoptotic cells, but remains cytoplasmic during G1 phase. Therefore, Rogner et al. (2000) considered it likely that NAP1L2 represents a class of tissue-specific factors interacting with chromatin to regulate neuronal cell proliferation.
Because mouse embryos with deletion of the Nap1l2 gene exhibit neural tube defects closely resembling spina bifida and anencephaly in humans, Rogner et al. (2002) analyzed X-linked familial and spontaneous cases of neural tube defects for sequence alterations in the NAP1L2 gene. They found no differences in familial cases; however, they identified a number of SNPs within the 5-prime region of NAP1L2 in both cases of spontaneous neural tube defects and normal controls. Most of these SNPs led to the replacement of guanidines or cytosines within a CpG island that is conserved between the human and the mouse promoter regions. In the mouse, demethylation in vitro activated Nap1l2 transcriptional activity, suggesting the importance of the CpG island in regulating the activity of this gene and the potential importance of the polymorphisms in modifying its transcriptional activity. The expression of the gene may therefore depend on the genetic/environmental factors frequently associated with neural tube defects.
Rogner, U. C., Danoy, P., Matsuda, F., Moore, G. E., Stanier, P., Avner, P. SNPs in the CpG island of NAP1L2: a possible link between DNA methylation and neural tube defects? Am. J. Med. Genet. 110: 208-214, 2002. [PubMed: 12116227] [Full Text: https://doi.org/10.1002/ajmg.10453]
Rogner, U. C., Spyropoulos, D. D., Le Novere, N., Changeux, J.-P., Avner, P. Control of neurulation by the nucleosome assembly protein-1-like 2. Nature Genet. 25: 431-435, 2000. [PubMed: 10932189] [Full Text: https://doi.org/10.1038/78124]
Rougeulle, C., Avner, P. Cloning and characterization of a murine brain specific gene Bpx and its human homologue lying within the Xic candidate region. Hum. Molec. Genet. 5: 41-49, 1996. [PubMed: 8789438] [Full Text: https://doi.org/10.1093/hmg/5.1.41]