Jong M T, Gray T A, Ji Y, Glenn C C, Saitoh S, Driscoll D J, Nicholls R D
Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, 10900 Euclid Avenue, Cleveland, OH 44106-4955, USA.
Hum Mol Genet. 1999 May;8(5):783-93. doi: 10.1093/hmg/8.5.783.
We describe a complex imprinted locus in chromosome 15q11-q13 that encodes two genes, ZNF127 and ZNF127AS. The ZNF127 gene encodes a protein with a RING (C3HC4) zinc-finger and multiple C3H zinc-finger motifs, the former being closely related to a protein from variola major virus, the smallpox etiological agent. These motifs allow prediction of ZNF127 function as a ribonucleoprotein. The intronless ZNF127 gene is expressed ubiquitously, but the entire coding sequence and 5' CpG island overlaps a second gene, ZNF127AS, that is transcribed from the antisense strand with a different transcript size and pattern of expression. Allele-specific analysis shows that ZNF127 is expressed only from the paternal allele. Consistent with this expression pattern, in the brain the ZNF127 5' CpG island is completely unmethylated on the paternal allele but methylated on the maternal allele. Analyses of adult testis, sperm and fetal oocytes demonstrates a gametic methylation imprint with unmethylated paternal germ cells. Recent findings indicate that ZNF127 is part of the coordinately regulated imprinted domain affected in Prader-Willi syndrome patients with imprinting mutations. Therefore, ZNF127 and ZNF127AS are novel imprinted genes that may be associated with some of the clinical features of the polygenic Prader-Willi syndrome.
我们描述了位于15号染色体q11 - q13区域的一个复杂的印记基因座，该基因座编码两个基因，即ZNF127和ZNF127AS。ZNF127基因编码一种具有RING（C3HC4）锌指和多个C3H锌指基序的蛋白质，前者与天花病原体——天花病毒的一种蛋白质密切相关。这些基序使得ZNF127的功能可被预测为核糖核蛋白。无内含子的ZNF127基因在全身广泛表达，但其整个编码序列和5'端CpG岛与另一个基因ZNF127AS重叠，ZNF127AS从反义链转录，具有不同的转录本大小和表达模式。等位基因特异性分析表明，ZNF127仅从父本等位基因表达。与这种表达模式一致，在大脑中，ZNF127的5'端CpG岛在父本等位基因上完全未甲基化，而在母本等位基因上甲基化。对成年睾丸、精子和胎儿卵母细胞的分析表明，父本生殖细胞未甲基化，存在配子甲基化印记。最近的研究结果表明，ZNF127是普拉德 - 威利综合征患者中受印记突变影响的协同调控印记域的一部分。因此，ZNF127和ZNF127AS是新的印记基因，可能与多基因普拉德 - 威利综合征的一些临床特征相关。
