Alexander Mary Kate, Mlynarczyk-Evans Susanna, Royce-Tolland Morgan, Plocik Alex, Kalantry Sundeep, Magnuson Terry, Panning Barbara
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
J Cell Biol. 2007 Oct 22;179(2):269-76. doi: 10.1083/jcb.200706053.
A number of mammalian genes are expressed from only one of the two homologous chromosomes, selected at random in each cell. These include genes subject to X-inactivation, olfactory receptor (OR) genes, and several classes of immune system genes. The means by which monoallelic expression is established are only beginning to be understood. Using a cytological assay, we show that the two homologous alleles of autosomal random monoallelic loci differ from each other in embryonic stem (ES) cells, before establishment of monoallelic expression. The Polycomb Group gene Eed is required to establish this distinctive behavior. In addition, we found that when Eed mutant ES cells are differentiated, they fail to establish asynchronous replication timing at OR loci. These results suggest a common mechanism for random monoallelic expression on autosomes and the X chromosome, and implicate Eed in establishing differences between homologous OR loci before and after differentiation.
许多哺乳动物基因仅从两条同源染色体中的一条表达，在每个细胞中随机选择。这些基因包括X染色体失活相关基因、嗅觉受体（OR）基因以及几类免疫系统基因。单等位基因表达确立的方式才刚刚开始被理解。通过细胞分析，我们发现常染色体随机单等位基因座的两个同源等位基因在胚胎干细胞（ES细胞）中，在单等位基因表达确立之前就彼此不同。多梳蛋白家族基因Eed是确立这种独特行为所必需的。此外，我们发现当Eed突变的ES细胞分化时，它们无法在OR基因座建立异步复制时间。这些结果表明常染色体和X染色体上随机单等位基因表达存在共同机制，并表明Eed在分化前后确立同源OR基因座之间的差异中起作用。
