Hu R J, Lee M P, Johnson L A, Feinberg A P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hum Mol Genet. 1996 Nov;5(11):1743-8. doi: 10.1093/hmg/5.11.1743.
Three genes on 11p15.5 are known to undergo genomic imprinting. The gene for insulin-like growth factor II (IGF2) is normally expressed from the paternal allele, while H19 and p57KIP2, a cyclin-dependent kinase inhibitor, are expressed from the maternal allele. Five germline balanced chromosomal rearrangement breakpoints from patients with Beckwith-Wiedemann syndrome (BWS) have been mapped to 11p15.5 between p57KIP2 and IGF2, and all are derived from the maternal chromosome. By positional cloning from BWS breakpoints, we have isolated a gene 100 kb and 65 kb centromeric to the proximal end of this BWS breakpoint cluster and p57KIP2, respectively. This gene is homologous to yeast nucleosome assembly protein (NAP1) and to a human homologue of NAP1, and we designate it hNAP2 (human nucleosome assembly protein 2). hNAP2 diverges in its expression pattern from IGF2, H19, and p57KIP2, and it shows biallelic expression in all tissues tested. Thus, hNAP2 is functionally insulated from the imprinting domain of 11p15.
已知位于11p15.5上的三个基因会发生基因组印记。胰岛素样生长因子II（IGF2）基因通常从父本等位基因表达，而H19和细胞周期蛋白依赖性激酶抑制剂p57KIP2则从母本等位基因表达。来自贝克威思-维德曼综合征（BWS）患者的五个种系平衡染色体重排断点已被定位到11p15.5上p57KIP2和IGF2之间，且均来自母本染色体。通过从BWS断点进行定位克隆，我们分别分离出了一个位于该BWS断点簇近端和p57KIP2着丝粒方向100 kb和65 kb处的基因。该基因与酵母核小体组装蛋白（NAP1）以及NAP1的一个人类同源物同源，我们将其命名为hNAP2（人类核小体组装蛋白2）。hNAP2在表达模式上与IGF2、H19和p57KIP2不同，并且在所有检测的组织中均表现为双等位基因表达。因此，hNAP2在功能上与11p15的印记结构域相隔离。
