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PMID: 8391636 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Dioxin receptor and C/EBP regulate the function of the glutathione S-transferase Ya gene xenobiotic response element.

Molecular and cellular biology ·Vol. 13 ·No. 7 ·1993-07-00 ·Pages 4365-73

Pimental RA, Liang B, Yee GK, Wilhelmsson A, Poellinger L, Paulson KE

Abstract

The rat glutathione S-transferase Ya gene xenobiotic response element (XRE) has both constitutive and xenobiotic-inducible activity. We present evidence that the XRE is regulated by both the constitutive C/EBP transcription factor and the xenobiotic-activated dioxin receptor. A ligand-activated XRE-binding protein was shown to be dioxin receptor by specific antibody immunodepletion and binding of highly purified receptor. Identification of C/EBP alpha as the constitutive binding protein was demonstrated by competition with a C/EBP binding site, protein-DNA cross-linking to determine the molecular weight of the constitutive protein(s), specific antibody immunodepletion, and binding of purified bacterially expressed C/EBP alpha. Mutational analysis of the XRE revealed that the constitutive factor (C/EBP alpha) shares a nearly identical overlapping binding site with the dioxin receptor. In functional testing of the putative C/EBP-XRE interaction, cotransfected C/EBP alpha activated an XRE test promoter in the non-xenobiotic-responsive HeLa cell line. Unexpectedly, cotransfected C/EBP alpha had no effect on basal activity but significantly increased the xenobiotic response of the XRE test promoter in the xenobiotic-responsive, C/EBP-positive HepG2 cell line. Furthermore, inhibition of C/EBP-binding protein(s) in HepG2 cells by transfection of C/EBP oligonucleotides suppressed the xenobiotic response. These results suggest that C/EBP alpha and dioxin receptor recognize the same DNA sequence element and that transcriptional regulation can occur by cooperative interactions between these two transcription factors.

Related Genes
Ya
MeSH Terms
Animals Base Sequence CCAAT-Enhancer-Binding Proteins Cell Line DNA DNA-Binding Proteins/metabolism Electrophoresis, Polyacrylamide Gel Gene Expression Regulation, Enzymologic Glutathione Transferase/genetics,metabolism HeLa Cells Humans Molecular Sequence Data Mutagenesis, Site-Directed Nuclear Proteins/metabolism Rats Receptors, Aryl Hydrocarbon Receptors, Drug/metabolism Xenobiotics
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Nuclear Proteins Receptors, Aryl Hydrocarbon Receptors, Drug Xenobiotics DNA Glutathione Transferase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pimental R A
USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.
Liang B
Yee G K
Wilhelmsson A
Poellinger L
Paulson K E
References (49)
49 references, click to expand
  1. Isolation of a recombinant copy of the gene encoding C/EBP.
    Genes Dev. 1988 Jul;2(7):786-800 PMID: 2850264
  2. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.
    Genes Dev. 1991 Sep;5(9):1538-52 PMID: 1840554
  3. The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite.
    Science. 1989 Mar 31;243(4899):1681-8 PMID: 2494700
  4. Co-localization of elements required for phorbol ester stimulation and glucocorticoid repression of proliferin gene expression.
    Genes Dev. 1989 Jun;3(6):760-9 PMID: 2744462
  5. Glutathione S-transferases: gene structure, regulation, and biological function.
    Annu Rev Biochem. 1989;58:743-64 PMID: 2673020
  6. The specific DNA binding activity of the dioxin receptor is modulated by the 90 kd heat shock protein.
    EMBO J. 1990 Jan;9(1):69-76 PMID: 2153080
  7. CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells.
    Genes Dev. 1989 Sep;3(9):1314-22 PMID: 2558052
  8. Activation of the dioxin and glucocorticoid receptors to a DNA binding state under cell-free conditions.
    J Biol Chem. 1990 Feb 5;265(4):2269-77 PMID: 2153679
  9. Analysis of the upstream elements of the xenobiotic compound-inducible and positionally regulated glutathione S-transferase Ya gene.
    Mol Cell Biol. 1990 May;10(5):1841-52 PMID: 2325638
  10. Jun-Fos and receptors for vitamins A and D recognize a common response element in the human osteocalcin gene.
    Cell. 1990 May 4;61(3):497-504 PMID: 2159384
  11. Regulation of glutathione S-transferase Ya subunit gene expression: identification of a unique xenobiotic-responsive element controlling inducible expression by planar aromatic compounds.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3826-30 PMID: 2160079
  12. Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action.
    Annu Rev Pharmacol Toxicol. 1990;30:251-77 PMID: 2188570
  13. Aryl hydrocarbon (Ah) receptor DNA-binding activity. Sequence specificity and Zn2+ requirement.
    J Biol Chem. 1990 Jun 5;265(16):9251-8 PMID: 2160969
  14. Evidence of changes in protease sensitivity and subunit exchange rate on DNA binding by C/EBP.
    Science. 1990 Aug 17;249(4970):771-4 PMID: 2202050
  15. Transcription factor interactions: selectors of positive or negative regulation from a single DNA element.
    Science. 1990 Sep 14;249(4974):1266-72 PMID: 2119054
  16. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP.
    Cell. 1990 Nov 2;63(3):643-53 PMID: 2171780
  17. Protein-DNA interactions at a dioxin-responsive enhancer. Evidence that the transformed Ah receptor is heteromeric.
    J Biol Chem. 1990 Nov 25;265(33):20708-12 PMID: 2173716
  18. Multiple DNA-binding factors interact with overlapping specificities at the aryl hydrocarbon response element of the cytochrome P450IA1 gene.
    Mol Cell Biol. 1990 Dec;10(12):6408-16 PMID: 2174107
  19. Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form.
    Mol Cell Biol. 1991 Jan;11(1):401-11 PMID: 1986235
  20. Ubiquitous transcription factor OTF-1 mediates induction of the MMTV promoter through synergistic interaction with hormone receptors.
    Cell. 1991 Feb 8;64(3):565-72 PMID: 1846780
  21. Cloning of a factor required for activity of the Ah (dioxin) receptor.
    Science. 1991 May 17;252(5008):954-8 PMID: 1852076
  22. The glucocorticoid receptor binds to a sequence overlapping the TATA box of the human osteocalcin promoter: a potential mechanism for negative regulation.
    Mol Cell Biol. 1991 Jun;11(6):3379-83 PMID: 2038339
  23. A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro.
    Genes Dev. 1991 Sep;5(9):1553-67 PMID: 1884998
  24. cAMP stimulates the C/EBP-related transcription factor rNFIL-6 to trans-locate to the nucleus and induce c-fos transcription.
    Genes Dev. 1991 Oct;5(10):1754-66 PMID: 1655570
  25. A liver-enriched transcriptional activator protein, LAP, and a transcriptional inhibitory protein, LIP, are translated from the same mRNA.
    Cell. 1991 Nov 1;67(3):569-79 PMID: 1934061
  26. RXR beta: a coregulator that enhances binding of retinoic acid, thyroid hormone, and vitamin D receptors to their cognate response elements.
    Cell. 1991 Dec 20;67(6):1251-66 PMID: 1662118
  27. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription.
    Genes Dev. 1992 Mar;6(3):439-53 PMID: 1547942
  28. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells.
    Mol Cell Biol. 1992 Apr;12(4):1708-18 PMID: 1312668
  29. Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation.
    Mol Cell Biol. 1992 Apr;12(4):1856-63 PMID: 1312672
  30. Dioxin- and Ah receptor-dependent protein binding to xenobiotic responsive elements and G-rich DNA studied by in vivo footprinting.
    J Biol Chem. 1992 Apr 5;267(10):6874-8 PMID: 1313025
  31. Calcium-regulated phosphorylation within the leucine zipper of C/EBP beta.
    Science. 1992 Apr 17;256(5055):370-3 PMID: 1314426
  32. cDNA cloning and structure of mouse putative Ah receptor.
    Biochem Biophys Res Commun. 1992 Apr 15;184(1):246-53 PMID: 1314586
  33. Mechanism of action of a repressor of dioxin-dependent induction of Cyp1a1 gene transcription.
    Mol Cell Biol. 1992 May;12(5):2115-23 PMID: 1314949
  34. A ubiquitous factor is required for C/EBP-related proteins to form stable transcription complexes on an albumin promoter segment in vitro.
    Genes Dev. 1992 Jun;6(6):991-1004 PMID: 1592265
  35. Mechanism of dioxin action: Ah receptor-mediated increase in promoter accessibility in vivo.
    Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4811-5 PMID: 1317573
  36. Multiple elements within the glucocorticoid regulatory unit of the rat alpha 1-acid glycoprotein gene are recognition sites for C/EBP.
    J Biol Chem. 1992 Jun 5;267(16):11111-9 PMID: 1597449
  37. Transcriptional repression by a novel member of the bZIP family of transcription factors.
    Mol Cell Biol. 1992 Jul;12(7):3070-7 PMID: 1620116
  38. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor.
    Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8185-9 PMID: 1325649
  39. Cross-coupling of signal transduction pathways: the dioxin receptor mediates induction of cytochrome P-450IA1 expression via a protein kinase C-dependent mechanism.
    Mol Cell Biol. 1993 Jan;13(1):677-89 PMID: 8380231
  40. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  41. Location of regulatory elements responsible for drug induction in the rat cytochrome P-450c gene.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8044-8 PMID: 3464941
  42. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins.
    Science. 1988 Jun 24;240(4860):1759-64 PMID: 3289117
  43. Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer.
    Science. 1988 Jul 15;241(4863):350-3 PMID: 2838908
  44. The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements.
    Cell. 1988 Jul 29;54(3):313-23 PMID: 3396073
  45. A DNA-binding factor specific for xenobiotic responsive elements of P-450c gene exists as a cryptic form in cytoplasm: its possible translocation to nucleus.
    Proc Natl Acad Sci U S A. 1988 Aug;85(16):5859-63 PMID: 3413062
  46. Retinoic acid and thyroid hormone induce gene expression through a common responsive element.
    Nature. 1988 Nov 17;336(6196):262-5 PMID: 2848197
  47. Xenobiotic regulation of glutathione S-transferase Ya gene expression.
    Mol Toxicol. 1989 Oct-Dec;2(4):215-35 PMID: 2490978
  48. Liver cells contain constitutive DNase I-hypersensitive sites at the xenobiotic response elements 1 and 2 (XRE1 and -2) of the rat cytochrome P-450IA1 gene and a constitutive, nuclear XRE-binding factor that is distinct from the dioxin receptor.
    Mol Cell Biol. 1991 Sep;11(9):4314-23 PMID: 1652054
  49. Vaccination against ovine cysticercosis using a defined recombinant antigen.
    Nature. 1989 Apr 13;338(6216):585-7 PMID: 2648160
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.7.4365-4373.1993
Published
1993-07-00
Pages
4365-73
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359997
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.7.4365-4373.1993 PMC Full Text View journal details
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