Home LiteratureArticle Details
PMID: 8223471 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Promoter, enhancer and silencer elements regulate rearrangement of an immunoglobulin transgene.

The EMBO journal ·Vol. 12 ·No. 12 ·1993-12-00 ·Pages 4615-23

Lauster R, Reynaud CA, Mårtensson IL, Peter A, Bucchini D, Jami J, Weill JC

Abstract

The chicken Ig lambda light chain locus is composed of a single V gene closely linked (1.8 kb) to a single J-C unit in its natural configuration. In mice transgenic for this locus, the transgene becomes rearranged in B cells and to a much lesser extent in T cells. Modifications were introduced in the transgene in order to characterize elements which target the recombinase to the Ig loci. In the absence of either the promoter or the enhancer located 3' of C lambda, rearrangement of the transgene is reduced 20- to 100-fold. Moreover, rearrangement is increased 5-fold when the DNA segment between V lambda and J lambda ('Uo segment'), which is deleted during the joining process, is replaced by a neutral DNA segment of equal length. The Uo segment behaved as a strong transcriptional silencer when tested in a CAT assay in vitro. Control transgenic mice harbouring only the two 3 bp mutations that introduced restriction sites at both ends of the Uo segment to allow for its replacement were also analysed. Rearrangement was reduced 10- to 100-fold in B cells from such transgenic lines. A model is proposed whereby the sites of these two mutations would function by counteracting transiently the repressing effect of the silencer, thus giving access of the chicken light chain locus to the recombinase.

MeSH Terms
Animals B-Lymphocytes Base Sequence Cell Line Chickens Cloning, Molecular DNA Enhancer Elements, Genetic Gene Rearrangement, B-Lymphocyte, Light Chain Immunoglobulin G/genetics Mice Mice, Transgenic Molecular Sequence Data Mutagenesis Polymerase Chain Reaction Promoter Regions, Genetic Regulatory Sequences, Nucleic Acid Transcription, Genetic
Chemicals
Immunoglobulin G DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lauster R
Basel Institute for Immunology, Switzerland.
Reynaud C A
Mårtensson I L
Peter A
Bucchini D
Jami J
Weill J C
References (53)
53 references, click to expand
  1. Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers.
    Cell. 1989 Nov 17;59(4):649-55 PMID: 2582491
  2. The duck beta-globin gene cluster contains a single enhancer element.
    FEBS Lett. 1988 Jul 18;234(2):300-4 PMID: 2839370
  3. Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate.
    EMBO J. 1990 Jan;9(1):117-25 PMID: 2153073
  4. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene.
    Cell. 1990 Apr 6;61(1):113-24 PMID: 2180582
  5. T-cell receptor gamma delta and gamma transgenic mice suggest a role of a gamma gene silencer in the generation of alpha beta T cells.
    Proc Natl Acad Sci U S A. 1990 Apr;87(8):3067-71 PMID: 2326267
  6. RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombination.
    Science. 1990 Jun 22;248(4962):1517-23 PMID: 2360047
  7. A novel enhancer in the immunoglobulin lambda locus is duplicated and functionally independent of NF kappa B.
    Genes Dev. 1990 Jun;4(6):978-92 PMID: 2116989
  8. Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes.
    Mol Cell Biol. 1990 Oct;10(10):5486-95 PMID: 2144610
  9. Selective expression of RAG-2 in chicken B cells undergoing immunoglobulin gene conversion.
    Cell. 1991 Jan 11;64(1):201-8 PMID: 1986866
  10. Silencing of the expression of the immunoglobulin kappa gene in non-B cells.
    Mol Cell Biol. 1991 Mar;11(3):1431-7 PMID: 1899907
  11. Molecular requirements for the mu-induced light chain gene rearrangement in pre-B cells.
    EMBO J. 1991 Aug;10(8):2147-55 PMID: 1712291
  12. Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion.
    Nature. 1992 Mar 12;356(6365):154-6 PMID: 1545868
  13. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement.
    Cell. 1992 Mar 6;68(5):855-67 PMID: 1547487
  14. RAG-1-deficient mice have no mature B and T lymphocytes.
    Cell. 1992 Mar 6;68(5):869-77 PMID: 1547488
  15. Identification of a cis-acting DNA antisilencer element which modulates vimentin gene expression.
    Mol Cell Biol. 1992 May;12(5):2230-40 PMID: 1569950
  16. VDJ recombination.
    Immunol Today. 1992 Aug;13(8):306-14 PMID: 1510813
  17. Emergence of committed B lymphoid progenitors in the developing chicken embryo.
    EMBO J. 1992 Dec;11(12):4349-58 PMID: 1425572
  18. Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues.
    J Exp Med. 1965 Nov 1;122(5):853-76 PMID: 4159057
  19. Isolation of high-molecular-weight DNA from mammalian cells.
    Eur J Biochem. 1973 Jul 2;36(1):32-8 PMID: 4200179
  20. Organization and reorganization of immunoglobulin genes in A-MULV-transformed cells: rearrangement of heavy but not light chain genes.
    Cell. 1981 Dec;27(2 Pt 1):381-90 PMID: 6277505
  21. Ordered rearrangement of immunoglobulin heavy chain variable region segments.
    EMBO J. 1984 Jun;3(6):1209-19 PMID: 6086308
  22. Transcription of T cell receptor beta-chain genes is controlled by a downstream regulatory element.
    EMBO J. 1988 Mar;7(3):745-50 PMID: 3396541
  23. A novel, inducible and T cell-specific enhancer located at the 3' end of the T cell receptor alpha locus.
    EMBO J. 1989 Mar;8(3):729-33 PMID: 2524381
  24. Selection for B cells with productive IgL gene rearrangements occurs in the bursa of Fabricius during chicken embryonic development.
    Genes Dev. 1989 Jun;3(6):838-47 PMID: 2501152
  25. A T-cell-specific transcriptional enhancer element 3' of C alpha in the human T-cell receptor alpha locus.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6714-8 PMID: 2788889
  26. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region.
    Cell. 1989 Oct 6;59(1):171-83 PMID: 2507167
  27. The immunoglobulin kappa locus contains a second, stronger B-cell-specific enhancer which is located downstream of the constant region.
    EMBO J. 1989 Jul;8(7):1959-64 PMID: 2507312
  28. A developmental-specific factor binds to suppressor sites flanking the immunoglobulin heavy-chain enhancer.
    Genes Dev. 1989 Aug;3(8):1255-66 PMID: 2792763
  29. A nuclear DNA attachment element mediates elevated and position-independent gene activity.
    Nature. 1989 Sep 28;341(6240):343-5 PMID: 2797152
  30. The surrogate light chain in B-cell development.
    Immunol Today. 1993 Feb;14(2):60-8 PMID: 8166770
  31. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161-5 PMID: 6438633
  32. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments.
    Cell. 1985 Feb;40(2):271-81 PMID: 2578321
  33. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity.
    Cell. 1985 Feb;40(2):283-91 PMID: 3917859
  34. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements.
    Cell. 1985 Jul;41(3):885-97 PMID: 3924411
  35. Cell-type preference of immunoglobulin kappa and lambda gene promoters.
    EMBO J. 1985 Nov;4(11):2831-8 PMID: 2998757
  36. Introduced T cell receptor variable region gene segments recombine in pre-B cells: evidence that B and T cells use a common recombinase.
    Cell. 1986 Jan 31;44(2):251-9 PMID: 3484682
  37. Rearrangement of chicken immunoglobulin genes is not an ongoing process in the embryonic bursa of Fabricius.
    Proc Natl Acad Sci U S A. 1986 May;83(10):3336-40 PMID: 3010290
  38. Counting components of the chicken's B cell system.
    Immunol Rev. 1986 Jun;91:115-28 PMID: 3488258
  39. Conservation and variation in the large scale organisation of the globin gene domains of duck and chicken.
    Mol Gen Genet. 1986 May;203(2):193-201 PMID: 3016478
  40. Recombination between immunoglobulin variable region gene segments is enhanced by transcription.
    Nature. 1986 Dec 11-17;324(6097):585-9 PMID: 3491327
  41. A hyperconversion mechanism generates the chicken light chain preimmune repertoire.
    Cell. 1987 Feb 13;48(3):379-88 PMID: 3100050
  42. Rearrangement of a chicken immunoglobulin gene occurs in the lymphoid lineage of transgenic mice.
    Nature. 1987 Mar 26-Apr 1;326(6111):409-11 PMID: 3031506
  43. B lymphocyte-specific protein binding near an immunoglobulin kappa-chain gene J segment.
    Proc Natl Acad Sci U S A. 1987 Mar;84(6):1516-20 PMID: 3104899
  44. Rearrangement and expression of rabbit immunoglobulin kappa light chain gene in transgenic mice.
    Proc Natl Acad Sci U S A. 1987 Jun;84(12):4229-33 PMID: 3108888
  45. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  46. Negative regulation contributes to tissue specificity of the immunoglobulin heavy-chain enhancer.
    Mol Cell Biol. 1987 Jul;7(7):2558-67 PMID: 3039350
  47. 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
  48. 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
  49. Transient gene expression in untransformed lymphocytes.
    Eur J Immunol. 1987 Oct;17(10):1499-502 PMID: 3479332
  50. Position-independent, high-level expression of the human beta-globin gene in transgenic mice.
    Cell. 1987 Dec 24;51(6):975-85 PMID: 3690667
  51. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains.
    EMBO J. 1987 Nov;6(11):3299-305 PMID: 3123216
  52. A transcriptional enhancer 3' of C beta 2 in the T cell receptor beta locus.
    Science. 1988 Jul 8;241(4862):205-8 PMID: 2968651
  53. The V(D)J recombination activating gene, RAG-1.
    Cell. 1989 Dec 22;59(6):1035-48 PMID: 2598259
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-12-00
Pages
4615-23
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413898
Subset
IM
External Links
PubMed source 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: [email protected]

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