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PMID: 7687740 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system.

Molecular and cellular biology ·Vol. 13 ·No. 8 ·1993-08-00 ·Pages 4531-8

Tanaka N, Kawakami T, Taniguchi T

Abstract

Interferon (IFN) regulatory factor 1 (IRF-1) and IRF-2 were originally identified as transcription factors involved in the regulation of the IFN system. IRF-1 functions as a transcriptional activator, while IRF-2 represses IRF-1 function. More recently, evidence has been provided that IRF-1 and IRF-2 manifest antioncogenic and oncogenic properties, respectively, and that loss of one or both of the IRF-1 alleles may be critical for the development of human hematopoietic neoplasms. Both factors show a high degree of structural similarity in their N-terminal DNA-binding domains, and previous studies suggested that IRF-1 and IRF-2 bind to similar or identical cis elements within type I IFN (IFN-alpha and -beta) and IFN-inducible genes. However, the exact recognition sequences of these two factors have not yet been determined; hence, the spectrum of the IRF-responsive genes remains unclear. In this study, we determined the DNA sequences recognized by IRF-1 and IRF-2, using a polymerase chain reaction-assisted DNA-binding site selection method. We report that sequences selected by this method and the affinities for each sequence were virtually indistinguishable between IRF-1 and IRF-2. We confirm the presence of two contiguous IRF recognition sequences within the promoter region of the IFN-beta gene and of at least one such sequence in all of the IFN-inducible genes examined. Furthermore, we report the presence of potential IRF sequences in the upstream region of several genes involved in cell growth control.

MeSH Terms
Base Sequence Binding Sites Binding, Competitive Cell Division DNA-Binding Proteins/genetics Gene Expression Regulation Humans In Vitro Techniques Interferon Regulatory Factor-1 Interferon Regulatory Factor-2 Interferons/physiology Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Phosphoproteins/genetics Regulatory Sequences, Nucleic Acid Repressor Proteins/genetics Transcription Factors/genetics
Chemicals
DNA-Binding Proteins IRF1 protein, human IRF2 protein, human Interferon Regulatory Factor-1 Interferon Regulatory Factor-2 Oligodeoxyribonucleotides Phosphoproteins Repressor Proteins Transcription Factors Interferons
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tanaka N
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kawakami T
Taniguchi T
References (64)
64 references, click to expand
  1. Critical role of a common transcription factor, IRF-1, in the regulation of IFN-beta and IFN-inducible genes.
    EMBO J. 1992 Jan;11(1):185-93 PMID: 1371248
  2. Characterization of the DNA binding domain of the mouse IRF-2 protein.
    Protein Eng. 1993 Feb;6(2):195-200 PMID: 8475044
  3. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins.
    Mol Cell Biol. 1992 Aug;12(8):3315-24 PMID: 1630447
  4. A transcription factor with SH2 and SH3 domains is directly activated by an interferon alpha-induced cytoplasmic protein tyrosine kinase(s).
    Cell. 1992 Jul 24;70(2):323-35 PMID: 1638633
  5. Interferon-dependent signaling pathways: DNA elements, transcription factors, mutations, and effects of viral proteins.
    J Interferon Res. 1992 Jun;12(3):147-51 PMID: 1379292
  6. p53 function and dysfunction.
    Cell. 1992 Aug 21;70(4):523-6 PMID: 1505019
  7. Biochemistry of interferons and their actions.
    Annu Rev Biochem. 1982;51:251-82 PMID: 6180680
  8. Induction of ppp(A2'p)nA-dependent RNase in murine JLS-V9R cells during growth inhibition.
    Proc Natl Acad Sci U S A. 1983 Aug;80(16):4954-8 PMID: 6576368
  9. The 5'-flanking sequence of human interferon-beta 1 gene is responsible for viral induction of transcription.
    Nucleic Acids Res. 1983 Aug 25;11(16):5403-12 PMID: 6310498
  10. Preparation and use of nuclease-treated rabbit reticulocyte lysates for the translation of eukaryotic messenger RNA.
    Methods Enzymol. 1983;96:50-74 PMID: 6656641
  11. Endogenous regulation of macrophage proliferative expansion by colony-stimulating factor-induced interferon.
    Science. 1984 Jan 13;223(4632):178-81 PMID: 6606850
  12. Growth regulation of a cellular tumour antigen, p53, in nontransformed cells.
    Nature. 1984 Mar 8-14;308(5955):199-201 PMID: 6366574
  13. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences.
    Nature. 1985 Apr 18-24;314(6012):637-9 PMID: 3990797
  14. Regulation of cell proliferation and differentiation by interferons.
    Biochem J. 1985 Mar 1;226(2):345-60 PMID: 2581554
  15. Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene.
    Nature. 1986 Aug 21-27;322(6081):743-6 PMID: 3748155
  16. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements.
    Cell. 1987 Jan 30;48(2):331-42 PMID: 3643061
  17. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1.
    Mol Cell Biol. 1987 Jan;7(1):273-80 PMID: 3494192
  18. Interferon-beta gene regulation: tandemly repeated sequences of a synthetic 6 bp oligomer function as a virus-inducible enhancer.
    Cell. 1987 May 8;49(3):357-67 PMID: 3032451
  19. A common positive trans-acting factor binds to enhancer sequences in the promoters of mouse H-2 and beta 2-microglobulin genes.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2653-7 PMID: 3554244
  20. Interferons and their actions.
    Annu Rev Biochem. 1987;56:727-77 PMID: 2441659
  21. The role of interferon-beta 1 and the 26-kDa protein (interferon-beta 2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor.
    J Immunol. 1987 Sep 15;139(6):1867-72 PMID: 3305707
  22. Interferon-induced transcription of a gene encoding a 15-kDa protein depends on an upstream enhancer element.
    Proc Natl Acad Sci U S A. 1987 Sep;84(18):6394-8 PMID: 3476954
  23. Interferons alpha and beta as cellular regulatory molecules.
    Interferon. 1987;9:13-74 PMID: 3316040
  24. Molecular cloning and structure of the human interleukin-5 gene.
    J Biol Chem. 1987 Dec 5;262(34):16580-4 PMID: 2824500
  25. Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.
    Mol Cell Biol. 1987 Oct;7(10):3723-31 PMID: 2824996
  26. New inducers revealed by the promoter sequence analysis of two interferon-activated human genes.
    Eur J Biochem. 1987 Dec 1;169(2):313-21 PMID: 3121313
  27. Synergistic interactions of interleukin 1, interferon-beta, and tumor necrosis factor in terminally differentiating a mouse myeloid leukemic cell line (M1). Evidence that interferon-beta is an autocrine differentiating factor.
    J Immunol. 1988 Jan 1;140(1):112-9 PMID: 3275716
  28. The 5' region of the human interleukin 4 gene: structure and potential regulatory elements.
    Nucleic Acids Res. 1988 Jan 25;16(2):772 PMID: 3257560
  29. Interferon-responsive regulatory elements in the promoter of the human 2',5'-oligo(A) synthetase gene.
    Mol Cell Biol. 1987 Dec;7(12):4498-504 PMID: 2830497
  30. Interferon response element of the human gene 6-16.
    EMBO J. 1988 Jan;7(1):85-92 PMID: 3359997
  31. Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.
    Genes Dev. 1988 Apr;2(4):383-93 PMID: 3371658
  32. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements.
    Cell. 1988 Sep 9;54(6):903-13 PMID: 3409321
  33. Two interferon-induced nuclear factors bind a single promoter element in interferon-stimulated genes.
    Proc Natl Acad Sci U S A. 1988 Nov;85(22):8521-5 PMID: 2460869
  34. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements.
    EMBO J. 1988 Nov;7(11):3397-405 PMID: 2850164
  35. Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter.
    Mol Cell Biol. 1988 Aug;8(8):3065-79 PMID: 2974922
  36. Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1.
    Nature. 1989 Jan 19;337(6204):270-2 PMID: 2911367
  37. Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression.
    Nucleic Acids Res. 1989 May 11;17(9):3335-46 PMID: 2566973
  38. Characterization of the human p53 gene promoter.
    Mol Cell Biol. 1989 May;9(5):2163-72 PMID: 2664471
  39. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes.
    Cell. 1989 Aug 25;58(4):729-39 PMID: 2475256
  40. Eukaryotic transcriptional regulatory proteins.
    Annu Rev Biochem. 1989;58:799-839 PMID: 2673023
  41. Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9936-40 PMID: 2557635
  42. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro.
    Genes Dev. 1989 Sep;3(9):1362-71 PMID: 2606351
  43. Different pathways mediate virus inducibility of the human IFN-alpha 1 and IFN-beta genes.
    Cell. 1990 Mar 9;60(5):767-79 PMID: 2107026
  44. Purification and cloning of interferon-stimulated gene factor 2 (ISGF2): ISGF2 (IRF-1) can bind to the promoters of both beta interferon- and interferon-stimulated genes but is not a primary transcriptional activator of either.
    Mol Cell Biol. 1990 Jun;10(6):2448-57 PMID: 2342456
  45. Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated.
    Cell. 1990 Oct 19;63(2):303-12 PMID: 2208287
  46. A sensitive method for the determination of protein-DNA binding specificities.
    Nucleic Acids Res. 1990 Nov 11;18(21):6197-204 PMID: 2243767
  47. Transcription factors induced by interferons alpha and gamma.
    Nucleic Acids Res. 1990 Nov 25;18(22):6573-80 PMID: 2123539
  48. Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons.
    Mol Cell Biol. 1991 Jan;11(1):182-91 PMID: 1898761
  49. Specific depletion of the B-cell population induced by aberrant expression of human interferon regulatory factor 1 gene in transgenic mice.
    Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):532-6 PMID: 1988951
  50. Direct interaction between Sp1 and the BPV enhancer E2 protein mediates synergistic activation of transcription.
    Cell. 1991 May 3;65(3):493-505 PMID: 1850324
  51. Organization of the murine and human interleukin-7 receptor genes: two mRNAs generated by differential splicing and presence of a type I-interferon-inducible promoter.
    Mol Cell Biol. 1991 Jun;11(6):3052-9 PMID: 2038316
  52. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role.
    Cell. 1991 Jul 12;66(1):107-19 PMID: 2070412
  53. Activation of IFN-beta element by IRF-1 requires a posttranslational event in addition to IRF-1 synthesis.
    Nucleic Acids Res. 1991 Aug 25;19(16):4421-8 PMID: 1886766
  54. The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element.
    Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11495-9 PMID: 1763063
  55. Purification, cloning, and RXR identity of the HeLa cell factor with which RAR or TR heterodimerizes to bind target sequences efficiently.
    Cell. 1992 Jan 24;68(2):377-95 PMID: 1310259
  56. Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element.
    Cell. 1992 Feb 7;68(3):597-612 PMID: 1339307
  57. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes.
    Proc Natl Acad Sci U S A. 1990 May;87(10):3743-7 PMID: 2111015
  58. Not more than 117 base pairs of 5'-flanking sequence are required for inducible expression of a human IFN-alpha gene.
    Nature. 1983 Jun 2-8;303(5916):439-42 PMID: 6304525
  59. Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase.
    Science. 1992 Sep 18;257(5077):1685-9 PMID: 1382315
  60. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system.
    Adv Immunol. 1992;52:263-81 PMID: 1442307
  61. Two domains of ISGF3 gamma that mediate protein-DNA and protein-protein interactions during transcription factor assembly contribute to DNA-binding specificity.
    Mol Cell Biol. 1993 Jan;13(1):196-206 PMID: 8417326
  62. Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia.
    Science. 1993 Feb 12;259(5097):968-71 PMID: 8438156
  63. Anti-oncogenic and oncogenic potentials of interferon regulatory factors-1 and -2.
    Science. 1993 Feb 12;259(5097):971-4 PMID: 8438157
  64. Interferon regulatory factor 1 is a myeloid differentiation primary response gene induced by interleukin 6 and leukemia inhibitory factor: role in growth inhibition.
    Cell Growth Differ. 1991 Aug;2(8):401-7 PMID: 1793735
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.8.4531-4538.1993
Published
1993-08-00
Pages
4531-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC360068
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.13.8.4531-4538.1993 PMC Full Text View journal details
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