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. 1989 Jul;9(7):2837–2846. doi: 10.1128/mcb.9.7.2837

Hormonal regulation of TSE1-repressed genes: evidence for multiple genetic controls in extinction.

M J Thayer 1, R E Fournier 1
PMCID: PMC362749  PMID: 2571076

Abstract

Somatic cell hybrids formed by fusing hepatoma cells with fibroblasts generally fail to express liver functions, a phenomenon termed extinction. Previous studies demonstrated that extinction of the genes encoding tyrosine aminotransferase, phosphoenolpyruvate carboxykinase, and argininosuccinate synthetase is mediated by a specific genetic locus (TSE1) that maps to mouse chromosome 11 and human chromosome 17. In this report, we show that full repression of these genes requires a genetic factor in addition to TSE1. This conclusion is based on the observation that residual gene activity was apparent in monochromosomal hybrids retaining human TSE1 but not in complex hybrids retaining many fibroblast chromosomes. Furthermore, TSE1-repressed genes were hormone inducible, whereas fully extinguished genes were not. Analysis of hybrid segregants indicated that genetic loci required for the complete repression phenotype were distinct from TSE1.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boney C., Fink D., Schlichter D., Carr K., Wicks W. D. Direct evidence that the protein kinase catalytic subunit mediates the effects of cAMP on tyrosine aminotransferase synthesis. J Biol Chem. 1983 Apr 25;258(8):4911–4918. [PubMed] [Google Scholar]
  2. Chen T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. doi: 10.1016/0014-4827(77)90089-1. [DOI] [PubMed] [Google Scholar]
  3. Chin A. C., Fournier R. E. A genetic analysis of extinction: trans-regulation of 16 liver-specific genes in hepatoma-fibroblast hybrid cells. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1614–1618. doi: 10.1073/pnas.84.6.1614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cowan N. J., Dobner P. R., Fuchs E. V., Cleveland D. W. Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions. Mol Cell Biol. 1983 Oct;3(10):1738–1745. doi: 10.1128/mcb.3.10.1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davidson R. L., Ephrussi B., Yamamoto K. Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization. Proc Natl Acad Sci U S A. 1966 Nov;56(5):1437–1440. doi: 10.1073/pnas.56.5.1437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davidson R. L. Gene expression in somatic cell hybrids. Annu Rev Genet. 1974;8:195–218. doi: 10.1146/annurev.ge.08.120174.001211. [DOI] [PubMed] [Google Scholar]
  8. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  9. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  10. Garcia Ruiz J. P., Ingram R., Hanson R. W. Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4189–4193. doi: 10.1073/pnas.75.9.4189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ghisalberti A. V., Steele J. G., Cake M. H., McGrath M. C., Oliver I. T. Role of adrenaline and cyclic AMP in appearance of tyrosine aminotransferase in perinatal rat liver. Biochem J. 1980 Sep 15;190(3):685–690. doi: 10.1042/bj1900685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holt P. G., Oliver I. T. Studies on the mechanism of induction of tyrosine aminotransferase in neonatal rat liver. Biochemistry. 1969 Apr;8(4):1429–1437. doi: 10.1021/bi00832a018. [DOI] [PubMed] [Google Scholar]
  13. Killary A. M., Fournier R. E. A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells. Cell. 1984 Sep;38(2):523–534. doi: 10.1016/0092-8674(84)90507-5. [DOI] [PubMed] [Google Scholar]
  14. Killary A. M., Lugo T. G., Fournier R. E. Isolation of thymidine kinase-deficient rat hepatoma cells by selection with bromodeoxyuridine, Hoechst 33258, and visible light. Biochem Genet. 1984 Apr;22(3-4):201–213. doi: 10.1007/BF00484224. [DOI] [PubMed] [Google Scholar]
  15. Lem J., Chin A. C., Thayer M. J., Leach R. J., Fournier R. E. Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7302–7306. doi: 10.1073/pnas.85.19.7302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Loose D. S., Shaw P. A., Krauter K. S., Robinson C., Englard S., Hanson R. W., Gluecksohn-Waelsch S. Trans regulation of the phosphoenolpyruvate carboxykinase (GTP) gene, identified by deletions in chromosome 7 of the mouse. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5184–5188. doi: 10.1073/pnas.83.14.5184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lugo T. G., Handelin B., Killary A. M., Housman D. E., Fournier R. E. Isolation of microcell hybrid clones containing retroviral vector insertions into specific human chromosomes. Mol Cell Biol. 1987 Aug;7(8):2814–2820. doi: 10.1128/mcb.7.8.2814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mathieu-Mahul D., Xu D. Q., Saule S., Lidereau R., Galibert F., Berger R., Mauchauffé M., Larsen C. J. An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus. Hum Genet. 1985;71(1):41–44. doi: 10.1007/BF00295666. [DOI] [PubMed] [Google Scholar]
  19. McCormick A., Wu D., Castrillo J. L., Dana S., Strobl J., Thompson E. B., Karin M. Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1. Cell. 1988 Oct 21;55(2):379–389. doi: 10.1016/0092-8674(88)90061-x. [DOI] [PubMed] [Google Scholar]
  20. Mével-Ninio M., Weiss M. C. Immunofluorescence analysis of the time-course of extinction, reexpression, and activation of albumin production in rat hepatoma-mouse fibroblast heterokaryons and hybrids. J Cell Biol. 1981 Aug;90(2):339–350. doi: 10.1083/jcb.90.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. PITOT H. C., PERAINO C., MORSE P. A., Jr, POTTER V. R. HEPATOMAS IN TISSUE CULTURE COMPARED WITH ADAPTING LIVER IN VIVO. Natl Cancer Inst Monogr. 1964 Apr;13:229–245. [PubMed] [Google Scholar]
  22. Peterson T. C., Killary A. M., Fournier R. E. Chromosomal assignment and trans regulation of the tyrosine aminotransferase structural gene in hepatoma hybrid cells. Mol Cell Biol. 1985 Sep;5(9):2491–2494. doi: 10.1128/mcb.5.9.2491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Petit C., Levilliers J., Ott M. O., Weiss M. C. Tissue-specific expression of the rat albumin gene: genetic control of its extinction in microcell hybrids. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2561–2565. doi: 10.1073/pnas.83.8.2561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Quinn P. G., Wong T. W., Magnuson M. A., Shabb J. B., Granner D. K. Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1988 Aug;8(8):3467–3475. doi: 10.1128/mcb.8.8.3467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Räihä N. C., Suihkonen J. Factors influencing the development of urea-synthesizing enzymes in rat liver. Biochem J. 1968 May;107(6):793–797. doi: 10.1042/bj1070793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. SERENI F., KENNEY F. T., KRETCHMER N. Factors influencing the development of tyrosine-alpha-ketoglutarate transaminase activity in rat liver. J Biol Chem. 1959 Mar;234(3):609–612. [PubMed] [Google Scholar]
  27. Sasaki K., Cripe T. P., Koch S. R., Andreone T. L., Petersen D. D., Beale E. G., Granner D. K. Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. J Biol Chem. 1984 Dec 25;259(24):15242–15251. [PubMed] [Google Scholar]
  28. Schmid E., Schmid W., Jantzen M., Mayer D., Jastorff B., Schütz G. Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes. Eur J Biochem. 1987 Jun 15;165(3):499–506. doi: 10.1111/j.1432-1033.1987.tb11467.x. [DOI] [PubMed] [Google Scholar]
  29. Schmid W., Müller G., Schütz G., Gluecksohn-Waelsch S. Deletions near the albino locus on chromosome 7 of the mouse affect the level of tyrosine aminotransferase mRNA. Proc Natl Acad Sci U S A. 1985 May;82(9):2866–2869. doi: 10.1073/pnas.82.9.2866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schneider J. A., Weiss M. C. Expression of differentiated functions in hepatoma cell hybrids. I. Tyrosine aminotransferase in hepatoma-fibroblast hybrids. Proc Natl Acad Sci U S A. 1971 Jan;68(1):127–131. doi: 10.1073/pnas.68.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Shinomiya T., Scherer G., Schmid W., Zentgraf H., Schütz G. Isolation and characterization of the rat tyrosine aminotransferase gene. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1346–1350. doi: 10.1073/pnas.81.5.1346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Short J. M., Wynshaw-Boris A., Short H. P., Hanson R. W. Characterization of the phosphoenolpyruvate carboxykinase (GTP) promoter-regulatory region. II. Identification of cAMP and glucocorticoid regulatory domains. J Biol Chem. 1986 Jul 25;261(21):9721–9726. [PubMed] [Google Scholar]
  33. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  34. Sparkes R. S., Weiss M. C. Expression of differentiated functions in hepatoma cell hybrids: alanine aminotransferase. Proc Natl Acad Sci U S A. 1973 Feb;70(2):377–381. doi: 10.1073/pnas.70.2.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Tripputi P., Guérin S. L., Moore D. D. Two mechanisms for the extinction of gene expression in hybrid cells. Science. 1988 Sep 2;241(4870):1205–1207. doi: 10.1126/science.2842865. [DOI] [PubMed] [Google Scholar]
  36. Weiss M. C., Chaplain M. Expression of differentiated functions in hepatoma cell hybrids: reappearance of tyrosine aminotransferase inducibility after the loss of chromosomes. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3026–3030. doi: 10.1073/pnas.68.12.3026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Weiss M. C., Sparkes R. S., Bertolotti R. Expression of differentiated functions in hepatoma cell hybrids: IX extinction and reexpression of liver-specific enzymes in rat hepatoma-Chinese hamster fibroblast hybrids. Somatic Cell Genet. 1975 Jan;1(1):27–40. doi: 10.1007/BF01538730. [DOI] [PubMed] [Google Scholar]
  38. Yamamoto K. R. Steroid receptor regulated transcription of specific genes and gene networks. Annu Rev Genet. 1985;19:209–252. doi: 10.1146/annurev.ge.19.120185.001233. [DOI] [PubMed] [Google Scholar]
  39. Yoo-Warren H., Monahan J. E., Short J., Short H., Bruzel A., Wynshaw-Boris A., Meisner H. M., Samols D., Hanson R. W. Isolation and characterization of the gene coding for cytosolic phosphoenolpyruvate carboxykinase (GTP) from the rat. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3656–3660. doi: 10.1073/pnas.80.12.3656. [DOI] [PMC free article] [PubMed] [Google Scholar]

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