Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 May;81(9):2650–2654. doi: 10.1073/pnas.81.9.2650

Structure of the 5' ends of immunoglobulin genes: a novel conserved sequence.

T G Parslow, D L Blair, W J Murphy, D K Granner
PMCID: PMC345127  PMID: 6425835

Abstract

Recent investigations have suggested that tissue-specific regulatory factors are required for immunoglobulin gene transcription. Cells of the mouse lymphocytoid pre-B-cell line 70Z/3 contain a constitutively rearranged immunoglobulin kappa light chain gene; the nucleotide sequence of this gene exhibits all the known properties of a functionally competent transcription unit. Nevertheless, transcripts derived from this gene are detectable only after exposure of the cells to bacterial lipopolysaccharide, implying that accurate DNA rearrangement is not sufficient to activate expression of the gene. Comparison of the sequence of the 70Z/3 kappa light chain gene with those encoding other immunoglobulin heavy and light chains has revealed that a distinctive promoter region structure is characteristic of this multigene family. The sequence A-T-T-T-G-C-A-T lies approximately 70 base pairs upstream from the site of transcriptional initiation in every light chain gene examined; in heavy chain genes, the corresponding location is occupied by the precise inverse (A-T-G-C-A-A-A-T) of this sequence. Although adjacent regions of DNA have diverged extensively in evolution, these octanucleotide sequences are stringently conserved at this location among diverse immunoglobulin genes from at least two mammalian species. The proximity of this conserved octanucleotide block to the site of transcriptional initiation suggests that it may serve as a recognition locus for factors regulating immunoglobulin gene expression in a tissue-specific fashion.

Full text

PDF
2651

Images in this article

2651Image
on p.2651

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altenburger W., Steinmetz M., Zachau H. G. Functional and non-functional joining in immunoglobulin light chain genes of a mouse myeloma. Nature. 1980 Oct 16;287(5783):603–607. doi: 10.1038/287603a0. [DOI] [PubMed] [Google Scholar]
  2. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  3. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
  4. Bentley D. L., Farrell P. J., Rabbitts T. H. Unrearranged immunoglobulin variable region genes have a functional promoter. Nucleic Acids Res. 1982 Mar 25;10(6):1841–1856. doi: 10.1093/nar/10.6.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  6. Chung S. Y., Folsom V., Wooley J. DNase I-hypersensitive sites in the chromatin of immunoglobulin kappa light chain genes. Proc Natl Acad Sci U S A. 1983 May;80(9):2427–2431. doi: 10.1073/pnas.80.9.2427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clarke C., Berenson J., Goverman J., Boyer P. D., Crews S., Siu G., Calame K. An immunoglobulin promoter region is unaltered by DNA rearrangement and somatic mutation during B-cell development. Nucleic Acids Res. 1982 Dec 11;10(23):7731–7749. doi: 10.1093/nar/10.23.7731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cohen J. B., Effron K., Rechavi G., Ben-Neriah Y., Zakut R., Givol D. Simple DNA sequences in homologous flanking regions near immunoglobulin VH genes: a role in gene interaction? Nucleic Acids Res. 1982 Jun 11;10(11):3353–3370. doi: 10.1093/nar/10.11.3353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Das H. K., Lawrance S. K., Weissman S. M. Structure and nucleotide sequence of the heavy chain gene of HLA-DR. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3543–3547. doi: 10.1073/pnas.80.12.3543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
  11. Falkner F. G., Zachau H. G. Expression of mouse immunoglobulin genes in monkey cells. Nature. 1982 Jul 15;298(5871):286–288. doi: 10.1038/298286a0. [DOI] [PubMed] [Google Scholar]
  12. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  13. Gruss P., Dhar R., Khoury G. Simian virus 40 tandem repeated sequences as an element of the early promoter. Proc Natl Acad Sci U S A. 1981 Feb;78(2):943–947. doi: 10.1073/pnas.78.2.943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Heinrich G., Traunecker A., Tonegawa S. Somatic mutation creates diversity in the major group of mouse immunoglobulin kappa light chains. J Exp Med. 1984 Feb 1;159(2):417–435. doi: 10.1084/jem.159.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hozumi N., Wu G. E., Murialdo H., Roberts L., Vetter D., Fife W. L., Whiteley M., Sadowski P. RNA splicing mutation in an aberrantly rearranged immunoglobulin lambda I gene. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7019–7023. doi: 10.1073/pnas.78.11.7019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kataoka T., Nikaido T., Miyata T., Moriwaki K., Honjo T. The nucleotide sequences of rearranged and germline immunoglobulin VH genes of a mouse myeloma MC101 and evolution of VH genes in mouse. J Biol Chem. 1982 Jan 10;257(1):277–285. [PubMed] [Google Scholar]
  17. Kelley D. E., Coleclough C., Perry R. P. Functional significance and evolutionary development of the 5'-terminal regions of immunoglobulin variable-region genes. Cell. 1982 Jun;29(2):681–689. doi: 10.1016/0092-8674(82)90184-2. [DOI] [PubMed] [Google Scholar]
  18. Maki R., Kearney J., Paige C., Tonegawa S. Immunoglobulin gene rearrangement in immature B cells. Science. 1980 Sep 19;209(4463):1366–1369. doi: 10.1126/science.6774416. [DOI] [PubMed] [Google Scholar]
  19. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  20. Max E. E., Maizel J. V., Jr, Leder P. The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse kappa immunoglobulin J and C region genes. J Biol Chem. 1981 May 25;256(10):5116–5120. [PubMed] [Google Scholar]
  21. Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Max E. E., Seidman J. G., Miller H., Leder P. Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene. Cell. 1980 Oct;21(3):793–799. doi: 10.1016/0092-8674(80)90442-0. [DOI] [PubMed] [Google Scholar]
  23. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  24. Nelson K. J., Mather E. L., Perry R. P. Lipopolysaccharide-induced transcription of the kappa immunoglobulin locus occurs on both alleles and is independent of methylation status. Nucleic Acids Res. 1984 Feb 24;12(4):1911–1923. doi: 10.1093/nar/12.4.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nishioka Y., Leder P. Organization and complete sequence of identical embryonic and plasmacytoma kappa V-region genes. J Biol Chem. 1980 Apr 25;255(8):3691–3694. [PubMed] [Google Scholar]
  26. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  27. Parslow T. G., Granner D. K. Chromatin changes accompany immunoglobulin kappa gene activation: a potential control region within the gene. Nature. 1982 Sep 30;299(5882):449–451. doi: 10.1038/299449a0. [DOI] [PubMed] [Google Scholar]
  28. Parslow T. G., Granner D. K. Structure of a nuclease-sensitive region inside the immunoglobin kappa gene: evidence for a role in gene regulation. Nucleic Acids Res. 1983 Jul 25;11(14):4775–4792. doi: 10.1093/nar/11.14.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Parslow T. G., Milburn G. L., Lynch R. G., Granner D. K. Suppressor T cell action inhibits the expression of an excluded immunoglobulin gene. Science. 1983 Jun 24;220(4604):1389–1391. doi: 10.1126/science.6222474. [DOI] [PubMed] [Google Scholar]
  30. Perry R. P., Kelley D. E., Coleclough C., Seidman J. G., Leder P., Tonegawa S., Matthyssens G., Weigert M. Transcription of mouse kappa chain genes: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1937–1941. doi: 10.1073/pnas.77.4.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Perry R. P., Kelley D. E. Immunoglobulin messenger RNAs in murine cell lines that have characteristics of immature B lymphocytes. Cell. 1979 Dec;18(4):1333–1339. doi: 10.1016/0092-8674(79)90243-5. [DOI] [PubMed] [Google Scholar]
  32. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  33. Seidman J. G., Leder P. The arrangement and rearrangement of antibody genes. Nature. 1978 Dec 21;276(5690):790–795. doi: 10.1038/276790a0. [DOI] [PubMed] [Google Scholar]
  34. Seidman J. G., Max E. E., Leder P. A kappa-immunoglobulin gene is formed by site-specific recombination without further somatic mutation. Nature. 1979 Aug 2;280(5721):370–375. doi: 10.1038/280370a0. [DOI] [PubMed] [Google Scholar]
  35. Selsing E., Storb U. Somatic mutation of immunoglobulin light-chain variable-region genes. Cell. 1981 Jul;25(1):47–58. doi: 10.1016/0092-8674(81)90230-0. [DOI] [PubMed] [Google Scholar]
  36. Stafford J., Queen C. Cell-type specific expression of a transfected immunoglobulin gene. Nature. 1983 Nov 3;306(5938):77–79. doi: 10.1038/306077a0. [DOI] [PubMed] [Google Scholar]
  37. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Van Ness B. G., Weigert M., Coleclough C., Mather E. L., Kelley D. E., Perry R. P. Transcription of the unrearranged mouse C kappa locus: sequence of the initiation region and comparison of activity with a rearranged V kappa-C kappa gene. Cell. 1981 Dec;27(3 Pt 2):593–602. doi: 10.1016/0092-8674(81)90401-3. [DOI] [PubMed] [Google Scholar]
  39. Wasylyk B., Wasylyk C., Augereau P., Chambon P. The SV40 72 bp repeat preferentially potentiates transcription starting from proximal natural or substitute promoter elements. Cell. 1983 Feb;32(2):503–514. doi: 10.1016/0092-8674(83)90470-1. [DOI] [PubMed] [Google Scholar]
  40. Weischet W. O., Glotov B. O., Schnell H., Zachau H. G. Differences in the nuclease sensitivity between the two alleles of the immunoglobulin kappa light chain genes in mouse liver and myeloma nuclei. Nucleic Acids Res. 1982 Jun 25;10(12):3627–3645. doi: 10.1093/nar/10.12.3627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wu G. E., Govindji N., Hozumi N., Murialdo H. Nucleotide sequence of a chromosomal rearranged lambda 2 immunoglobulin gene of mouse. Nucleic Acids Res. 1982 Jul 10;10(13):3831–3843. doi: 10.1093/nar/10.13.3831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES