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IMPT1,一种与多特异性转运蛋白和多药耐药基因相似的印记基因。

IMPT1, an imprinted gene similar to polyspecific transporter and multi-drug resistance genes.

作者信息

Dao D, Frank D, Qian N, O'Keefe D, Vosatka R J, Walsh C P, Tycko B

机构信息

Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

出版信息

Hum Mol Genet. 1998 Apr;7(4):597-608. doi: 10.1093/hmg/7.4.597.

Abstract

Human chromosome 11p15.5 and distal mouse chromosome 7 include a megabase-scale chromosomal domain with multiple genes subject to parental imprinting. Here we describe mouse and human versions of a novel imprinted gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi-drug resistance pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues with metabolite transport functions, including liver, kidney, intestine, extra-embryonic membranes and placenta, and there is strongly preferential expression of the maternal allele in various mouse tissues at fetal stages. In post-natal tissues there is persistent expression, but the allelic bias attenuates. An allelic expression bias is also observed in human fetal and post-natal tissues, but there is significant interindividual variation and rare somatic allele switching. The fact that Impt1 is relatively repressed on the paternal allele, together with data from other imprinted genes, allows a statistical conclusion that the primary effect of human chromosome 11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative repression of genes on the paternal homolog. Dosage regulation of the metabolite transporter gene(s) by imprinting might regulate placental and fetal growth.

摘要

人类染色体11p15.5和小鼠远端染色体7包含一个百万碱基规模的染色体结构域,其中有多个基因受亲本印记影响。在此,我们描述了一个新的印记基因IMPT1的小鼠和人类版本,它位于IPL和p57 KIP2之间,编码一种预测的多跨膜蛋白,类似于细菌和真核生物的多特异性代谢物转运蛋白及多药耐药泵。小鼠Impt1和人类IMPT1 mRNA在具有代谢物转运功能的组织中高度表达,包括肝脏、肾脏、肠道、胚外膜和胎盘,并且在胎儿期的各种小鼠组织中,母本等位基因有强烈的优先表达。在出生后的组织中存在持续表达,但等位基因偏差减弱。在人类胎儿和出生后的组织中也观察到等位基因表达偏差,但存在显著的个体间差异和罕见的体细胞等位基因转换。Impt1在父本等位基因上相对受抑制这一事实,连同来自其他印记基因的数据,使得我们能够从统计学上得出结论:人类染色体11p15.5/小鼠远端染色体7印记的主要效应是全结构域范围内对父本同源染色体上基因的相对抑制。通过印记对代谢物转运蛋白基因进行剂量调节可能会调控胎盘和胎儿的生长。

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