TY - JOUR
T1 - A genetic analysis of extinction
T2 - Trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells
AU - Killary, A. M.
AU - Fournier, R. E.K.
N1 - Funding Information:
We are grateful to many colleagues for valuable drscussions thorughout the course of thus work, and to R. Maxson and M. Karin for critically reading the manuscript. We thank M. C. Weiss for provrding the hepatoma cell lines FIX?-5 and Faza 967, G Schutz for TAT cDNA clone pcTAT-3, and A. S. Lee for plasmid p3C5. The valuable technical assistance of F. R. Parker and M M. Smith is acknowledged. These studies were supported by grant GM26449 from the Natronal Institute of General Medical Scrences. A. M. K. received postdoctoral support from the Amerrcan Cancer Society, California Drvision and from the National Institutes of Health. R. E. K. F. is the recrpient of an American Cancer Society Faculty Research Award.
PY - 1984/9
Y1 - 1984/9
N2 - 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.
AB - 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.
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U2 - 10.1016/0092-8674(84)90507-5
DO - 10.1016/0092-8674(84)90507-5
M3 - Review article
C2 - 6147198
AN - SCOPUS:0021133977
SN - 0092-8674
VL - 38
SP - 523
EP - 534
JO - Cell
JF - Cell
IS - 2
ER -