Killary A M, Fournier R E
Cell. 1984 Sep;38(2):523-34. doi: 10.1016/0092-8674(84)90507-5.
Extinction is an operational term that refers to the lack of expression of tissue-specific traits that is generally observed in hybrid cells formed by fusing dissimilar cell types. To define the genetic basis of this phenomenon, a series of rat hepatoma x mouse fibroblast hybrids has been isolated and characterized. We report here that the extinction of hepatic marker traits in these clones was strictly correlated with the retention of five particular fibroblast chromosomes (autosomes 8, 9, 10, 11, and 13). In order to dissect this correlation into its component parts, hepatoma microcell hybrids containing single, specific fibroblast chromosomes were constructed. Hepatoma clones retaining only fibroblast chromosome 11 were specifically extinguished for liver-specific tyrosine aminotransferase (TAT) expression, while expression of four other hepatic traits and of numerous constitutive markers was unaffected. Furthermore, removal of fibroblast chromosome 11 from the populations by back-selection resulted in reexpression of TAT activity to full parental levels. These data define and localize a genetic locus, tissue-specific extinguisher-1 (Tse-1), which regulates hepatic TAT expression in trans. We also provide evidence that human Tse-1 resides on the homologous chromosome (human chromosome 17), and that hybrids retaining active Tse-1 loci lack TAT-specific mRNA.
消减是一个操作性术语，指的是在由不同细胞类型融合形成的杂种细胞中通常观察到的组织特异性性状表达的缺失。为了确定这一现象的遗传基础，一系列大鼠肝癌细胞与小鼠成纤维细胞的杂种已被分离并进行了表征。我们在此报告，这些克隆中肝脏标记性状的消减与五条特定的成纤维细胞染色体（常染色体8、9、10、11和13）的保留严格相关。为了将这种相关性分解为其组成部分，构建了含有单一特定成纤维细胞染色体的肝癌微细胞杂种。仅保留成纤维细胞染色体11的肝癌克隆，其肝脏特异性酪氨酸转氨酶（TAT）表达被特异性消减，而其他四种肝脏性状以及许多组成性标记的表达则未受影响。此外，通过回选从群体中去除成纤维细胞染色体11导致TAT活性重新表达至亲本的完整水平。这些数据定义并定位了一个遗传位点，即组织特异性消减因子-1（Tse-1），它以反式作用调节肝脏TAT的表达。我们还提供证据表明，人类Tse-1位于同源染色体（人类染色体17）上，并且保留活跃Tse-1位点的杂种缺乏TAT特异性mRNA。
