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PMID: 14762167 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

B cell development and immunoglobulin transcription in Oct-1-deficient mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 7 ·2004-02-17 ·Pages 2005-10

Wang VE, Tantin D, Chen J, Sharp PA

Abstract

The POU domain transcription factors Oct-1 and Oct-2 interact with the octamer element, a motif conserved within Ig promoters and enhancers, and mediate transcription from the Ig loci. Inactivation of Oct-2 by gene targeting results in normal B cell development and Ig transcription. To study the role of Oct-1 in these processes, the lymphoid compartment of RAG-1(-/-) animals was reconstituted with Oct-1-deficient fetal liver hematopoietic cells. Recipient mice develop B cells with levels of surface Ig expression comparable with wild type, although at slightly reduced numbers. These B cells transcribe Ig normally, respond to antigenic stimulation, undergo class switching, and use a normal repertoire of light chain variable segments. However, recipient mice show slight reductions in serum IgM and IgA. Thus, the Oct-1 protein is dispensable for B cell development and Ig transcription.

MeSH Terms
Adoptive Transfer Animals B-Lymphocytes/cytology,immunology,metabolism Cell Division Cell Line, Transformed DNA-Binding Proteins/deficiency,genetics,metabolism Embryo, Mammalian/embryology,metabolism Gene Deletion Gene Expression Regulation/genetics Genes, RAG-1/genetics Host Cell Factor C1 Immunoglobulin Heavy Chains/biosynthesis,genetics Immunoglobulin Light Chains/biosynthesis,genetics Immunoglobulins/biosynthesis,blood,genetics Mice Mice, Knockout Octamer Transcription Factor-1 Phenotype Transcription Factors/deficiency,genetics,metabolism Transcription, Genetic/genetics
Chemicals
DNA-Binding Proteins Hcfc1 protein, mouse Host Cell Factor C1 Immunoglobulin Heavy Chains Immunoglobulin Light Chains Immunoglobulins Octamer Transcription Factor-1 Pou2f1 protein, mouse Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wang Victoria E H
Department of Biology and Center for Cancer Research and McGovern Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139-4307, USA.
Tantin Dean
Chen Jianzhu
Sharp Phillip A
References (62)
62 references, click to expand
  1. Transcriptional regulation of the murine 3' IgH enhancer by OCT-2.
    Immunity. 1999 Nov;11(5):517-26 PMID: 10591177
  2. 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
  3. B cell development and immunoglobulin gene transcription in the absence of Oct-2 and OBF-1.
    Nat Immunol. 2001 Jan;2(1):69-74 PMID: 11135581
  4. Oct-2 regulates CD36 gene expression via a consensus octamer, which excludes the co-activator OBF-1.
    Nucleic Acids Res. 2002 Apr 15;30(8):1767-73 PMID: 11937630
  5. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence.
    Proc Natl Acad Sci U S A. 1984 May;81(9):2650-4 PMID: 6425835
  6. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements.
    Nature. 1984 Jul 5-11;310(5972):71-4 PMID: 6330567
  7. Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that includes a functional consensus sequence.
    Cell. 1985 Jun;41(2):479-87 PMID: 3921262
  8. 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
  9. Nuclear factor III, a novel sequence-specific DNA-binding protein from HeLa cells stimulating adenovirus DNA replication.
    Nature. 1986 Aug 14-20;322(6080):656-9 PMID: 3748145
  10. 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
  11. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes.
    Nature. 1986 Oct 16-22;323(6089):640-3 PMID: 3095662
  12. Multiple sequence elements are required for maximal in vitro transcription of a human histone H2B gene.
    Mol Cell Biol. 1986 Oct;6(10):3329-40 PMID: 3025588
  13. Mutational analysis of the immunoglobulin heavy chain promoter region.
    Proc Natl Acad Sci U S A. 1986 Dec;83(24):9626-30 PMID: 3099286
  14. The conserved decanucleotide from the immunoglobulin heavy chain promoter induces a very high transcriptional activity in B-cells when introduced into an heterologous promoter.
    EMBO J. 1987 Jun;6(6):1685-90 PMID: 3111845
  15. 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
  16. Multiple DNA sequence elements are necessary for the function of an immunoglobulin heavy chain promoter.
    Proc Natl Acad Sci U S A. 1987 Nov;84(21):7634-8 PMID: 3118372
  17. 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
  18. Binding of transcription factors to the promoter of the human U1 RNA gene studied by footprinting.
    J Biol Chem. 1988 Nov 25;263(33):17603-10 PMID: 3182863
  19. 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
  20. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein.
    Nature. 1988 Dec 8;336(6199):551-7 PMID: 2904654
  21. The POU domain is a bipartite DNA-binding structure.
    Nature. 1988 Dec 8;336(6199):601-4 PMID: 2904656
  22. Octamer-binding proteins from B or HeLa cells stimulate transcription of the immunoglobulin heavy-chain promoter in vitro.
    Genes Dev. 1988 Oct;2(10):1227-37 PMID: 3264542
  23. 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
  24. Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription.
    Cell. 1989 Sep 8;58(5):1001-7 PMID: 2505932
  25. A family of POU-domain and Pit-1 tissue-specific transcription factors in pituitary and neuroendocrine development.
    Annu Rev Physiol. 1990;52:773-91 PMID: 2184776
  26. The promoter of the human interleukin-2 gene contains two octamer-binding sites and is partially activated by the expression of Oct-2.
    Mol Cell Biol. 1990 Oct;10(10):5464-72 PMID: 2204815
  27. Complex pattern of immunoglobulin mu gene expression in normal and transgenic mice: nonoverlapping regulatory sequences govern distinct tissue specificities.
    Genes Dev. 1991 Jun;5(6):932-43 PMID: 1904384
  28. RAG-1-deficient mice have no mature B and T lymphocytes.
    Cell. 1992 Mar 6;68(5):869-77 PMID: 1547488
  29. Mini-Oct and Oct-2c: two novel, functionally diverse murine Oct-2 gene products are differentially expressed in the CNS.
    Neuron. 1992 Mar;8(3):541-58 PMID: 1550677
  30. Identification of sites for distinct DNA binding proteins including Oct-1 and Oct-2 in the Cr2 gene.
    J Immunol. 1992 Jun 1;148(11):3610-7 PMID: 1534100
  31. The C/EBP family of transcriptional activators is functionally important for Ig VH promoter activity in vivo and in vitro.
    J Immunol. 1992 Nov 15;149(10):3225-31 PMID: 1431100
  32. Targeted insertion of a variable region gene into the immunoglobulin heavy chain locus.
    Science. 1993 Nov 19;262(5137):1268-71 PMID: 8235657
  33. Positive and negative regulation of IL-2 gene expression: role of multiple regulatory sites.
    Cytokine. 1994 May;6(3):221-8 PMID: 8054477
  34. Octamer factors exert a dual effect on the IL-2 and IL-4 promoters.
    J Immunol. 1994 Dec 15;153(12):5572-85 PMID: 7989759
  35. Involvement of the Ets family factor PU.1 in the activation of immunoglobulin promoters.
    J Biol Chem. 1995 Jan 13;270(2):898-907 PMID: 7822329
  36. A B-cell coactivator of octamer-binding transcription factors.
    Nature. 1995 Jan 26;373(6512):360-2 PMID: 7779176
  37. OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins.
    Cell. 1995 Feb 10;80(3):497-506 PMID: 7859290
  38. Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation.
    Immunity. 1994 Nov;1(8):635-45 PMID: 7600291
  39. Cloning, functional characterization, and mechanism of action of the B-cell-specific transcriptional coactivator OCA-B.
    Mol Cell Biol. 1995 Aug;15(8):4115-24 PMID: 7623806
  40. Identification of CD36 as the first gene dependent on the B-cell differentiation factor Oct-2.
    Genes Dev. 1995 Jul 1;9(13):1598-607 PMID: 7543064
  41. The B-cell-specific transcription coactivator OCA-B/OBF-1/Bob-1 is essential for normal production of immunoglobulin isotypes.
    Nature. 1996 Oct 10;383(6600):542-7 PMID: 8849728
  42. Cloning and analysis of the human Pax-5 gene promoter.
    Biochem Biophys Res Commun. 1996 Nov 1;228(1):159-64 PMID: 8912652
  43. B lymphocytes are impaired in mice lacking the transcriptional co-activator Bob1/OCA-B/OBF1.
    Eur J Immunol. 1996 Dec;26(12):3214-8 PMID: 8977324
  44. B cell development under the condition of allelic inclusion.
    Immunity. 1997 Mar;6(3):225-33 PMID: 9075923
  45. Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells.
    Science. 1997 Jul 11;277(5323):221-5 PMID: 9211847
  46. Identification of target genes of the lymphoid-specific transcription factor Oct2.
    Immunobiology. 1997 Dec;198(1-3):217-26 PMID: 9442393
  47. oct-2 gene disruption eliminates the peritoneal B-1 lymphocyte lineage and attenuates B-2 cell maturation and function.
    J Immunol. 1997 Dec 1;159(11):5273-84 PMID: 9548466
  48. Transcriptional regulation during B cell development.
    Annu Rev Immunol. 1998;16:163-200 PMID: 9597128
  49. The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus.
    J Exp Med. 1998 Dec 7;188(11):2151-62 PMID: 9841928
  50. p53 mediates apoptotic crisis in primary Abelson virus-transformed pre-B cells.
    Mol Cell Biol. 1999 Jul;19(7):4825-31 PMID: 10373532
  51. The variable genes and gene families of the mouse immunoglobulin kappa locus.
    Eur J Immunol. 1999 Jul;29(7):2072-81 PMID: 10427969
  52. The DNA binding specificity of the bipartite POU domain and its subdomains.
    EMBO J. 1992 Dec;11(13):4993-5003 PMID: 1361172
  53. Restoration of T cell development in RAG-2-deficient mice by functional TCR transgenes.
    Science. 1993 Feb 5;259(5096):822-5 PMID: 8430336
  54. Cell type- and stage-specific expression of the CD20/B1 antigen correlates with the activity of a diverged octamer DNA motif present in its promoter.
    J Biol Chem. 1993 Mar 15;268(8):5949-56 PMID: 7680653
  55. Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival.
    Genes Dev. 1993 Apr;7(4):570-82 PMID: 8096198
  56. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development.
    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4528-32 PMID: 8506294
  57. Targeted disruption of the Oct-2 locus in a B cell provides genetic evidence for two distinct cell type-specific pathways of octamer element-mediated gene activation.
    EMBO J. 1993 Jul;12(7):2763-72 PMID: 8334992
  58. Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus.
    EMBO J. 1993 Dec;12(12):4635-45 PMID: 8223473
  59. OcaB is required for normal transcription and V(D)J recombination of a subset of immunoglobulin kappa genes.
    Cell. 2002 Sep 6;110(5):575-85 PMID: 12230975
  60. Embryonic lethality, decreased erythropoiesis, and defective octamer-dependent promoter activation in Oct-1-deficient mice.
    Mol Cell Biol. 2004 Feb;24(3):1022-32 PMID: 14729950
  61. Transcription of a gene for human U1 small nuclear RNA.
    Cell. 1982 May;29(1):265-74 PMID: 6179630
  62. Interaction and functional interference of C/EBPbeta with octamer factors in immunoglobulin gene transcription.
    Eur J Immunol. 2000 Jan;30(1):174-84 PMID: 10602039
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0307304101
Published
2004-02-17
Epub
2004-00-04
Pages
2005-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC357042
Subset
IM
Grants
NCI NIH HHS · P01 CA042063 · United States
NCI NIH HHS · P30 CA014051 · United States
NCI NIH HHS · P30-CA14051 · United States
PHS HHS · A140416 · United States
NCI NIH HHS · P01-CA42063 · United States
External Links
PubMed source DOI: 10.1073/pnas.0307304101 PMC Full Text View journal details
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