Home LiteratureArticle Details
PMID: 2571076 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Molecular and cellular biology ·Vol. 9 ·No. 7 ·1989-07-00 ·Pages 2837-46

Thayer MJ, Fournier RE

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.

MeSH Terms
Animals Argininosuccinate Synthase/genetics Blotting, Northern Bucladesine/pharmacology Chromosomes, Human, Pair 17 Cyclic AMP/physiology Cycloheximide/pharmacology DNA/drug effects,genetics DNA Probes Dexamethasone/pharmacology Fibroblasts/metabolism Fluorescent Antibody Technique Hormones/physiology Humans Hybrid Cells Ligases/genetics Liver/cytology,metabolism Phosphoenolpyruvate Carboxykinase (GTP)/genetics RNA, Messenger/biosynthesis,genetics Rats Regulatory Sequences, Nucleic Acid Tyrosine Transaminase/genetics
Chemicals
DNA Probes Hormones RNA, Messenger Bucladesine Dexamethasone DNA Cycloheximide Cyclic AMP Tyrosine Transaminase Phosphoenolpyruvate Carboxykinase (GTP) Ligases Argininosuccinate Synthase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Thayer M J
Department of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Fournier R E
References (39)
39 references, click to expand
  1. Role of adrenaline and cyclic AMP in appearance of tyrosine aminotransferase in perinatal rat liver.
    Biochem J. 1980 Sep 15;190(3):685-90 PMID: 6110423
  2. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain.
    Exp Cell Res. 1977 Feb;104(2):255-62 PMID: 65285
  3. Expression of differentiated functions in hepatoma cell hybrids: alanine aminotransferase.
    Proc Natl Acad Sci U S A. 1973 Feb;70(2):377-81 PMID: 4346888
  4. Studies on the mechanism of induction of tyrosine aminotransferase in neonatal rat liver.
    Biochemistry. 1969 Apr;8(4):1429-37 PMID: 4389942
  5. 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):127-31 PMID: 4395684
  6. Gene expression in somatic cell hybrids.
    Annu Rev Genet. 1974;8:195-218 PMID: 4613257
  7. 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):7302-6 PMID: 2902627
  8. Two mechanisms for the extinction of gene expression in hybrid cells.
    Science. 1988 Sep 2;241(4870):1205-7 PMID: 2842865
  9. 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):9721-6 PMID: 3015903
  10. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  11. Extinction of growth hormone expression in somatic cell hybrids involves repression of the specific trans-activator GHF-1.
    Cell. 1988 Oct 21;55(2):379-89 PMID: 3167985
  12. 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):339-50 PMID: 7026571
  13. Isolation and characterization of the rat tyrosine aminotransferase gene.
    Proc Natl Acad Sci U S A. 1984 Mar;81(5):1346-50 PMID: 6143318
  14. 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):5184-8 PMID: 3460089
  15. 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):3026-30 PMID: 4399833
  16. Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions.
    Mol Cell Biol. 1983 Oct;3(10):1738-45 PMID: 6646120
  17. 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 PMID: 17164
  18. Factors influencing the development of tyrosine-alpha-ketoglutarate transaminase activity in rat liver.
    J Biol Chem. 1959 Mar;234(3):609-12 PMID: 13641269
  19. 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):4911-8 PMID: 6131900
  20. Factors influencing the development of urea-synthesizing enzymes in rat liver.
    Biochem J. 1968 May;107(6):793-7 PMID: 16742604
  21. Detection of specific sequences among DNA fragments separated by gel electrophoresis.
    J Mol Biol. 1975 Nov 5;98(3):503-17 PMID: 1195397
  22. Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development.
    Proc Natl Acad Sci U S A. 1978 Sep;75(9):4189-93 PMID: 212740
  23. Steroid receptor regulated transcription of specific genes and gene networks.
    Annu Rev Genet. 1985;19:209-52 PMID: 3909942
  24. HEPATOMAS IN TISSUE CULTURE COMPARED WITH ADAPTING LIVER IN VIVO.
    Natl Cancer Inst Monogr. 1964 Apr;13:229-45 PMID: 14143233
  25. Chromosomal assignment and trans regulation of the tyrosine aminotransferase structural gene in hepatoma hybrid cells.
    Mol Cell Biol. 1985 Sep;5(9):2491-4 PMID: 2874483
  26. 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):1614-8 PMID: 2882508
  27. 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):2866-9 PMID: 2859594
  28. Identification of basal and cyclic AMP regulatory elements in the promoter of the phosphoenolpyruvate carboxykinase gene.
    Mol Cell Biol. 1988 Aug;8(8):3467-75 PMID: 2850495
  29. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping.
    Methods Enzymol. 1980;65(1):718-49 PMID: 6154876
  30. Isolation of microcell hybrid clones containing retroviral vector insertions into specific human chromosomes.
    Mol Cell Biol. 1987 Aug;7(8):2814-20 PMID: 2823107
  31. Isolation of thymidine kinase-deficient rat hepatoma cells by selection with bromodeoxyuridine, Hoechst 33258, and visible light.
    Biochem Genet. 1984 Apr;22(3-4):201-13 PMID: 6203516
  32. Transcription activation of the tyrosine aminotransferase gene by glucocorticoids and cAMP in primary hepatocytes.
    Eur J Biochem. 1987 Jun 15;165(3):499-506 PMID: 2885194
  33. Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin.
    J Biol Chem. 1984 Dec 25;259(24):15242-51 PMID: 6096365
  34. Regulation of pigment synthesis in mammalian cells, as studied by somatic hybridization.
    Proc Natl Acad Sci U S A. 1966 Nov;56(5):1437-40 PMID: 5230304
  35. 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):2561-5 PMID: 3458217
  36. A genetic analysis of extinction: trans-dominant loci regulate expression of liver-specific traits in hepatoma hybrid cells.
    Cell. 1984 Sep;38(2):523-34 PMID: 6147198
  37. 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):3656-60 PMID: 6304730
  38. Transcriptional control in the production of liver-specific mRNAs.
    Cell. 1981 Mar;23(3):731-9 PMID: 7226226
  39. An EcoRI restriction fragment length polymorphism (RFLP) in the human c-erb A locus.
    Hum Genet. 1985;71(1):41-4 PMID: 2993156
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.9.7.2837-2846.1989
Published
1989-07-00
Pages
2837-46
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC362749
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.9.7.2837-2846.1989 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2