Cell
Volume 33, Issue 3, July 1983, Pages 729-740
Journal home page for Cell

Article
A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes

https://doi.org/10.1016/0092-8674(83)90015-6Get rights and content

Abstract

Transcriptional enhancers, originally discovered in viral genomes, are short, cis-acting, regulatory sequences that strongly stimulate transcription from promoters of nearby genes. We demonstrate the existence of an enhancer within a mouse immunoglobulin heavy chain gene. A DNA fragment located between the joining region and the switch recombination region in the intron upstream of the immunoglobulin μ constant region has been linked, in both orientations, to genes coding for rabbit β-globin or SV40 T antigen. This element enhances the number of correct β-globin gene transcripts by at least two orders of magnitude and also stimulates production of T antigen. It acts from several hundred to several thousand base pairs up or downstream of a promoter without amplifying template copy number. Of the various cell lines tested, the immunoglobulin gene enhancer functions only in lymphocyte-derived (myeloma) cells. We propose that this tissue-specific enhancer contributes to the activation of somatically rearranged immunoglobulin variable region genes and possibly to abnormal expression of other genes (e.g. c-myc) that become translocated to its domain of influence.

References (71)

  • M.A.T. Muskavitch et al.

    An expandable gene that encodes a Drosophila glue protein is not expressed in variants lacking remote upstream sequences

    Cell

    (1982)
  • B.G. Neel et al.

    Avian leukosis virus-induced tumors have common proviral integration sites and synthesize discrete new RNAs: oncogenesis by promoter insertion

    Cell

    (1981)
  • R. Nusse et al.

    Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome

    Cell

    (1982)
  • J. Rogers et al.

    Two mRNAs with different 3′ ends encode membrane-bound and secreted forms of immunoglobulin μ chain

    Cell

    (1980)
  • G.L.C. Shen-Ong et al.

    Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas

    Cell

    (1982)
  • B.G. Van Ness et al.

    Transcription of the unrearranged mouse Cκ locus: sequence of the initiation region and comparison of activity with a rearranged Vκ-Cκ gene

    Cell

    (1981)
  • J. Vieira et al.

    The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers

    Gene

    (1982)
  • B. Wasylyk et al.

    The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements

    Cell

    (1983)
  • H. Weber et al.

    Modification of the rabbit chromosomal β-globin gene by restructuring and site-directed mutagenesis

  • F.W. Alt et al.

    Immunoglobulin heavy-chain expression and class switching in a murine leukemia cell line

    Nature

    (1982)
  • F.W. Alt et al.

    Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines

    Mol. Cell. Biol.

    (1982)
  • J. Banerji et al.

    Transient expression of cloned genes in mammalian cells

  • C. Benoist et al.

    In vivo sequence requirements of the SV40 early promoter region

    Nature

    (1981)
  • S.Y. Chung et al.

    DNase I hypersensitive sites in the chromatin of immunoglobulin kappa light chain genes

  • C. Clarke et al.

    An immunoglobulin promoter region is unaltered by DNA rearrangement and somatic mutation during B-cell development

    Nucl. Acids Res.

    (1982)
  • S. Cory et al.

    Interchromosomal recombination of the cellular oncogene c-myc with the immunoglobulin heavy chain locus in murine plasmacytomas is a reciprocal exchange

    EMBO J.

    (1983)
  • C. Cremisi

    The appearance of DNase I hypersensitive sites at the 5′ end of the late SV40 genes is correlated with the transcriptional switch

    Nucl. Acids Res.

    (1981)
  • M.M. Davis et al.

    An immunoglobulin heavy-chain gene is formed by at least two recombinational events

    Nature

    (1980)
  • J. de Villiers et al.

    A small segment of polyoma virus DNA enhances the expression of a cloned rabbit β-globin gene over a distance of at least 1400 base pairs

    Nucl. Acids Res.

    (1981)
  • J. de Villiers et al.

    Transcriptional “enhancers” from papovaviruses as components of eukaryotic expression vectors

  • J. de Villiers et al.

    Analysis of the transcriptional “enhancer” effect

  • J. de Villiers et al.

    Transcriptional “enhancers” from SV40 and polyoma virus show a cell type preference

    Nucl. Acids Res.

    (1982)
  • S. Fazekas de St. Groth et al.

    Production of monoclonal antibodies: strategy and tactics

    J. Immunol. Meth.

    (1980)
  • N.M. Gough et al.

    Sequences of the joining region for immunoglobulin heavy chains and their role in generation of antibody diversity

  • Cited by (805)

    View all citing articles on Scopus
    View full text