Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA.
Cell Rep. 2013 Mar 28;3(3):960-7. doi: 10.1016/j.celrep.2013.02.002. Epub 2013 Feb 28.
Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.
基因组印记导致一组基因中母本或父本等位基因的优先表达。印记对于哺乳动物的发育至关重要，其失调会导致许多疾病。然而，对于大多数印记基因，其在细胞水平上的印记功能相关性还知之甚少。我们使用小鼠的双标记马赛克分析（MADM）来创建单亲二体（UPD），并以单细胞分辨率可视化印记效应。虽然 12 号染色体 UPD 没有产生可检测的表型，但 7 号染色体 UPD 导致肝脏和肺部的父本生长优势非常显著，但在大脑或心脏中没有。7 号染色体上编码分泌性胰岛素样生长因子 2（IGF2）的单个基因，占父本优势效应的大部分。马赛克分析表明 7 号染色体上的其他印记位点以细胞自主的方式传递 IGF2 信号。我们的研究揭示了基因组印记效应的染色体和细胞类型特异性。
