Logo of biochemjBJ Latest papers and much more!
Biochem J. Mar 1, 2001; 354(Pt 2): 431–438.
PMCID: PMC1221672

Transcription factor AP-4 is a ligand for immunoglobulin-kappa promoter E-box elements.


Immunoglobulin (Ig)-kappa promoters from humans and mice share conserved sequences. The octamer element is common to all Ig promoters and pivotal for their function. However, other conserved sequence motifs, that differ between Ig variable gene families, are required for normal promoter function. These conserved motifs do not stimulate transcription in the absence of an octamer. One example is an E-box of the E47/E12 type (5'-CAGCTG-3'), which is found in all promoters of the human and murine Ig-kappa gene subgroups/families, with the exception of subgroups II and VI and their related murine families. In the present study we show that the ubiquitously expressed transcription factor AP-4, and not E47, interacts specifically with the kappa promoter E-boxes when tested in electrophoretic mobility-shift assays using nuclear extracts derived from human and murine B-cell lines. Furthermore, AP-4, unlike E47, did not act as a transactivator, which is in agreement with previous studies on intact kappa promoters, showing that transcription is absent when the octamer element has been mutated. Based on these data, and the conservation of the 5'-CAGCTG-3' motif among human and murine kappa promoters, we propose that AP-4 is the major ligand for Ig-kappa promoter E-boxes.

Full Text

The Full Text of this article is available as a PDF (248K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Strohal R, Helmberg A, Kroemer G, Kofler R. Mouse Vk gene classification by nucleic acid sequence similarity. Immunogenetics. 1989;30(6):475–493. [PubMed]
  • Schäble KF, Zachau HG. The variable genes of the human immunoglobulin kappa locus. Biol Chem Hoppe Seyler. 1993 Nov;374(11):1001–1022. [PubMed]
  • Falkner FG, Zachau HG. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. [PubMed]
  • Bemark M, Liberg D, Leanderson T. Conserved sequence elements in K promoters from mice and humans: implications for transcriptional regulation and repertoire expression. Immunogenetics. 1998;47(3):183–195. [PubMed]
  • Matthias P. Lymphoid-specific transcription mediated by the conserved octamer site: who is doing what? Semin Immunol. 1998 Apr;10(2):155–163. [PubMed]
  • Bergman Y, Rice D, Grosschedl R, Baltimore D. Two regulatory elements for immunoglobulin kappa light chain gene expression. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7041–7045. [PMC free article] [PubMed]
  • Wirth T, Staudt L, Baltimore D. An octamer oligonucleotide upstream of a TATA motif is sufficient for lymphoid-specific promoter activity. Nature. 1987 Sep 10;329(6135):174–178. [PubMed]
  • Eaton S, Calame K. 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):7634–7638. [PMC free article] [PubMed]
  • Sigvardsson M, Bemark M, Leanderson T. Stimulation of kappa transcription by a decamer-dependent, synergistic mechanism. Eur J Immunol. 1995 Jan;25(1):298–301. [PubMed]
  • Högbom E, Magnusson AC, Leanderson T. Functional modularity in the SP6 kappa promoter. Nucleic Acids Res. 1991 Aug 25;19(16):4347–4354. [PMC free article] [PubMed]
  • Blackwell TK, Weintraub H. Differences and similarities in DNA-binding preferences of MyoD and E2A protein complexes revealed by binding site selection. Science. 1990 Nov 23;250(4984):1104–1110. [PubMed]
  • Schlissel M, Voronova A, Baltimore D. Helix-loop-helix transcription factor E47 activates germ-line immunoglobulin heavy-chain gene transcription and rearrangement in a pre-T-cell line. Genes Dev. 1991 Aug;5(8):1367–1376. [PubMed]
  • Choi JK, Shen CP, Radomska HS, Eckhardt LA, Kadesch T. E47 activates the Ig-heavy chain and TdT loci in non-B cells. EMBO J. 1996 Sep 16;15(18):5014–5021. [PMC free article] [PubMed]
  • Sigvardsson M. Overlapping expression of early B-cell factor and basic helix-loop-helix proteins as a mechanism to dictate B-lineage-specific activity of the lambda5 promoter. Mol Cell Biol. 2000 May;20(10):3640–3654. [PMC free article] [PubMed]
  • Sigvardsson M, Bemark M, Leanderson T. Pentadecamer-binding proteins: definition of two independent protein-binding sites needed for functional activity. Mol Cell Biol. 1995 Mar;15(3):1343–1352. [PMC free article] [PubMed]
  • Bemark M, Leanderson T. Diverse transcription factors are involved in the quantitative regulation of transcriptional activation of kappa promoters. Eur J Immunol. 1997 Jun;27(6):1308–1318. [PubMed]
  • Ou SH, Garcia-Martínez LF, Paulssen EJ, Gaynor RB. Role of flanking E box motifs in human immunodeficiency virus type 1 TATA element function. J Virol. 1994 Nov;68(11):7188–7199. [PMC free article] [PubMed]
  • Liberg D, Sigvardsson M, Bemark M, Leanderson T. Differentiation-specific, octamer-dependent costimulation of kappa transcription. J Immunol. 1998 Apr 15;160(8):3899–3907. [PubMed]
  • Hu YF, Lüscher B, Admon A, Mermod N, Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990 Oct;4(10):1741–1752. [PubMed]
  • Mermod N, Williams TJ, Tjian R. Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 1988 Apr 7;332(6164):557–561. [PubMed]
  • King-Jones K, Korge G, Lehmann M. The helix-loop-helix proteins dAP-4 and daughterless bind both in vitro and in vivo to SEBP3 sites required for transcriptional activation of the Drosophila gene Sgs-4. J Mol Biol. 1999 Aug 6;291(1):71–82. [PubMed]
  • Schreiber E, Matthias P, Müller MM, Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. [PMC free article] [PubMed]
  • Parslow TG, Blair DL, Murphy WJ, Granner DK. Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence. Proc Natl Acad Sci U S A. 1984 May;81(9):2650–2654. [PMC free article] [PubMed]
  • Sigvardsson M, Leanderson T. Positive transcriptional control elements within the SP6 kappa promoter decamer 3' flanking sequence. Mol Immunol. 1994 Sep;31(13):1005–1016. [PubMed]
  • Liberg D, Sigvardsson M, Leanderson T. Oct proteins are qualitative rather than quantitative regulators of kappa transcription. Mol Immunol. 1997 Oct;34(14):979–986. [PubMed]
  • Atchison ML, Delmas V, Perry RP. A novel upstream element compensates for an ineffectual octamer motif in an immunoglobulin V kappa promoter. EMBO J. 1990 Oct;9(10):3109–3117. [PMC free article] [PubMed]
  • Schwarzenbach H, Newell JW, Matthias P. Involvement of the Ets family factor PU.1 in the activation of immunoglobulin promoters. J Biol Chem. 1995 Jan 13;270(2):898–907. [PubMed]
  • Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. [PubMed]
  • Bemark M, Olsson H, Heinegård D, Leanderson T. Purification and characterization of a protein binding to the SP6 kappa promoter. A potential role for CArG-box binding factor-A in kappa transcription. J Biol Chem. 1998 Jul 24;273(30):18881–18890. [PubMed]
  • Fodor E, Weinrich SL, Meister A, Mermod N, Rutter WJ. A pancreatic exocrine cell factor and AP4 bind overlapping sites in the amylase 2A enhancer. Biochemistry. 1991 Aug 20;30(33):8102–8108. [PubMed]
  • Comb M, Mermod N, Hyman SE, Pearlberg J, Ross ME, Goodman HM. Proteins bound at adjacent DNA elements act synergistically to regulate human proenkephalin cAMP inducible transcription. EMBO J. 1988 Dec 1;7(12):3793–3805. [PMC free article] [PubMed]
  • Friez M, Hermansen R, Milavetz B. Chromatin structure of the simian virus 40 late promoter: a deletional analysis. J Virol. 1999 Mar;73(3):1990–1997. [PMC free article] [PubMed]
  • Unk I, Kiss-Toth E, Boros I. Transcription factor AP-4 participates in activation of bovine leukemia virus long terminal repeat by p34 Tax. Nucleic Acids Res. 1994 Nov 25;22(23):4872–4875. [PMC free article] [PubMed]
  • Badinga L, Song S, Simmen RC, Simmen FA. A distal regulatory region of the insulin-like growth factor binding protein-2 (IGFBP-2) gene interacts with the basic helix-loop-helix transcription factor, AP-4. Endocrine. 1998 Jun;8(3):281–289. [PubMed]
  • Cui Y, Narayanan CS, Zhou J, Kumar A. Exon-I is involved in positive as well as negative regulation of human angiotensinogen gene expression. Gene. 1998 Dec 11;224(1-2):97–107. [PubMed]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...