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PMID: 2107075 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Extinction of Ig genes expression in myeloma x fibroblast somatic cell hybrids is accompanied by repression of the oct-2 gene encoding a B-cell specific transcription factor.

The EMBO journal ·Vol. 9 ·No. 3 ·1990-03-00 ·Pages 849-55

Bergman Y, Strich B, Sharir H, Ber R, Laskov R

Abstract

In most instances, fusion of differentiated cell types with fibroblasts has resulted in the extinction of differentiation-specific traits of the nonfibroblast parental cell. To explore the genetic basis of this phenomenon, we have used a series of somatic cell hybrids between myeloma cells and fibroblasts. Previous findings show that in these hybrids expression of the immunoglobulin (Ig) genes was extinguished at the transcriptional level. Our present results show that NF-kappa B transcription factor, known to be critical for kappa-chain enhancer activity, is present although in a lower amount, in the nucleus and in the cytosolic fraction of most of these hybrids (probably attached to the previously postulated I-kappa B inhibitor). In contrast, the expression of the NF-A2/OTF-2 transcription factor encoded by the oct-2 gene, which binds to the octameric motif located in the Ig promoters and heavy chain gene enhancer, is extinguished at the transcriptional level. Our data thus suggest that extinction of Ig genes expression occurs via an indirect mechanism in which a fibroblast factor suppresses transcription factor(s) which are critical for Ig transcription.

MeSH Terms
Animals B-Lymphocytes/immunology Base Sequence Cell Line Enhancer Elements, Genetic Fibroblasts/immunology Gene Expression Regulation Genes, Immunoglobulin Hybrid Cells/immunology Immunoglobulin Heavy Chains/genetics Immunoglobulin kappa-Chains/genetics L Cells/immunology Mice Molecular Sequence Data Multiple Myeloma/immunology Oligonucleotide Probes Plasmids Promoter Regions, Genetic Transcription Factors/genetics
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin kappa-Chains Oligonucleotide Probes Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Bergman Y
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Strich B
Sharir H
Ber R
Laskov R
References (56)
56 references, click to expand
  1. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes.
    Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331-5 PMID: 2494663
  2. Functional analysis of the murine IgH enhancer: evidence for negative control of cell-type specificity.
    Nucleic Acids Res. 1986 Oct 24;14(20):8209-21 PMID: 3095795
  3. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B.
    Nature. 1989 May 4;339(6219):70-3 PMID: 2654643
  4. Interleukin 1 and cyclic AMP induce kappa immunoglobulin light-chain expression via activation of an NF-kappa B-like DNA-binding protein.
    Mol Cell Biol. 1989 Mar;9(3):959-64 PMID: 2542770
  5. Role of the octamer motif in hybrid cell extinction of immunoglobulin gene expression: extinction is dominant in a two enhancer system.
    Cell. 1989 Aug 11;58(3):441-8 PMID: 2547524
  6. Regulation of melanin synthesis in mammalian cells, as studied by somatic hybridization. I. Evidence for negative control.
    J Cell Physiol. 1968 Oct;72(2):115-27 PMID: 4971858
  7. IgG synthesis in hybrid cells from an antibody-producing mouse myeloma and an L cell substrain.
    Nature. 1970 Dec 12;228(5276):1086-7 PMID: 5483162
  8. 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
  9. Suppression of immunoglobulin synthesis by cellular hybridization.
    Nat New Biol. 1971 May 19;231(20):87-90 PMID: 4103301
  10. Expression of tyrosine aminotransferase activity in somatic-cell heterokaryons: evidence for negative control of enzyme expression.
    Proc Natl Acad Sci U S A. 1971 Oct;68(10):2589-93 PMID: 4109409
  11. Expression of differentiated functions in hepatoma cell hybrids. VI. Extinction and re-expression of liver alcohol dehydrogenase.
    Biochimie. 1972;54(2):195-201 PMID: 4343793
  12. Use of somatic cell hybrids for analysis of the differentiated state.
    Bacteriol Rev. 1973 Jun;37(2):197-214 PMID: 4581783
  13. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor.
    Cell. 1988 Apr 22;53(2):211-7 PMID: 3129195
  14. Genes activated in the presence of an immunoglobulin enhancer or promoter are negatively regulated by a T-lymphoma cell line.
    Mol Cell Biol. 1988 May;8(5):1932-9 PMID: 3133550
  15. Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif.
    Science. 1988 Jul 29;241(4865):577-80 PMID: 3399892
  16. Two mechanisms for the extinction of gene expression in hybrid cells.
    Science. 1988 Sep 2;241(4870):1205-7 PMID: 2842865
  17. 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
  18. 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
  19. I kappa B: a specific inhibitor of the NF-kappa B transcription factor.
    Science. 1988 Oct 28;242(4878):540-6 PMID: 3140380
  20. Both immunoglobulin promoter and enhancer sequences are targets for suppression in myeloma-fibroblast hybrid cells.
    EMBO J. 1988 Oct;7(10):3093-8 PMID: 3141146
  21. Loss of growth hormone production following hybridization of a functional rat pituitary cell strain with a mouse fibroblast line.
    Exp Cell Res. 1971 Dec;69(2):336-44 PMID: 5170772
  22. Gene expression in somatic cell hybrids.
    Annu Rev Genet. 1974;8:195-218 PMID: 4613257
  23. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system.
    Nucleic Acids Res. 1981 Jul 10;9(13):3047-60 PMID: 6269071
  24. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis.
    Nucleic Acids Res. 1981 Dec 11;9(23):6505-25 PMID: 6275366
  25. Isolation and characterization of rat skeletal muscle and cytoplasmic actin genes.
    Proc Natl Acad Sci U S A. 1982 May;79(9):2763-7 PMID: 6953429
  26. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  27. Immunoglobulin gene transcription is activated by downstream sequence elements.
    Cell. 1983 Jul;33(3):741-8 PMID: 6409419
  28. Methylation status and DNase I sensitivity of immunoglobulin genes: changes associated with rearrangement.
    Proc Natl Acad Sci U S A. 1983 Aug;80(15):4689-93 PMID: 6308642
  29. A lymphocyte-specific enhancer in the mouse immunoglobulin kappa gene.
    Nature. 1984 Jan 5-11;307(5946):80-2 PMID: 6419128
  30. Fine mapping of an immunoglobulin gene activator.
    Mol Cell Biol. 1984 Jun;4(6):1042-9 PMID: 6330526
  31. 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
  32. Two regulatory elements for immunoglobulin kappa light chain gene expression.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7041-5 PMID: 6438631
  33. Cell-type preference of immunoglobulin kappa and lambda gene promoters.
    EMBO J. 1985 Nov;4(11):2831-8 PMID: 2998757
  34. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells.
    Nature. 1988 Dec 8;336(6199):544-51 PMID: 2904653
  35. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein.
    Nature. 1988 Dec 8;336(6199):551-7 PMID: 2904654
  36. Extinction of expression of the translocated myc gene in somatic cell hybrids between mouse myeloma and L-cells.
    Int J Cancer. 1989 Jan 15;43(1):87-92 PMID: 2492015
  37. Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor.
    Science. 1989 Jan 27;243(4890):544-6 PMID: 2536195
  38. The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains.
    Genes Dev. 1988 Dec;2(12A):1570-81 PMID: 3265124
  39. Repression of the immunoglobulin heavy chain enhancer by the adenovirus-2 E1A products.
    Science. 1985 Dec 20;230(4732):1391-4 PMID: 2999984
  40. A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.
    Nature. 1986 Jan 9-15;319(6049):154-8 PMID: 3079885
  41. A labile inhibitor blocks immunoglobulin kappa-light-chain-gene transcription in a pre-B leukemic cell line.
    Proc Natl Acad Sci U S A. 1986 Jan;83(2):295-8 PMID: 3079910
  42. 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
  43. The immunoglobulin heavy-chain B-lymphocyte enhancer efficiently stimulates transcription in non-lymphoid cells.
    EMBO J. 1986 Mar;5(3):553-60 PMID: 3011412
  44. Multiple nuclear factors interact with the immunoglobulin enhancer sequences.
    Cell. 1986 Aug 29;46(5):705-16 PMID: 3091258
  45. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism.
    Cell. 1986 Dec 26;47(6):921-8 PMID: 3096580
  46. A transcription factor which binds to the enhancers of SV40, immunoglobulin heavy chain and U2 snRNA genes.
    Nature. 1987 Jan 15-21;325(6101):268-72 PMID: 3027566
  47. Extinction of expression of immunoglobulin genes in myeloma X fibroblast somatic cell hybrids.
    Mol Cell Biol. 1987 Feb;7(2):936-9 PMID: 3102948
  48. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility.
    Science. 1987 Jun 19;236(4808):1573-7 PMID: 3109035
  49. An octamer oligonucleotide upstream of a TATA motif is sufficient for lymphoid-specific promoter activity.
    Nature. 1987 Sep 10-16;329(6135):174-8 PMID: 3627254
  50. Identification and purification of a human lymphoid-specific octamer-binding protein (OTF-2) that activates transcription of an immunoglobulin promoter in vitro.
    Cell. 1987 Dec 4;51(5):783-93 PMID: 3119226
  51. A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer.
    Genes Dev. 1987 Dec;1(10):1147-60 PMID: 2828167
  52. Localization of a repressive sequence contributing to B-cell specificity in the immunoglobulin heavy-chain enhancer.
    Mol Cell Biol. 1988 Feb;8(2):988-92 PMID: 2832747
  53. Interaction of a common factor with conserved promoter and enhancer sequences in histone H2B, immunoglobulin, and U2 small nuclear RNA (snRNA) genes.
    Proc Natl Acad Sci U S A. 1986 Sep;83(17):6382-6 PMID: 3462701
  54. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences.
    Nature. 1986 Oct 9-15;323(6088):548-51 PMID: 3093895
  55. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes.
    Nature. 1986 Oct 16-22;323(6089):640-3 PMID: 3095662
  56. Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA).
    EMBO J. 1988 Dec 20;7(13):4221-9 PMID: 3072196
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1990-03-00
Pages
849-55
Language
English
Region
England
NLM ID
8208664
PMCID
PMC551745
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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