Skip to main content
NCBI 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
. 1987 Oct;84(20):7019–7023. doi: 10.1073/pnas.84.20.7019

Identification of a DNA binding protein that recognizes the nonamer recombinational signal sequence of immunoglobulin genes.

B D Halligan 1, S V Desiderio 1
PMCID: PMC299220  PMID: 3118358

Abstract

Extracts of nuclei from B- and T-lymphoid cells contain a protein that binds specifically to the conserved nonamer DNA sequence within the recombinational signals of immunoglobulin genes. Complexes with DNA fragments from four kappa light-chain joining (J) segments have the same electrophoretic mobility. Nonamer-containing DNA fragments from heavy-chain and light-chain genes compete for binding. Within the 5'-flanking DNA of the J kappa 4 gene segment, the binding site has been localized to a 27-base-pair interval spanning the nonamer region. The binding activity is recovered as a single peak after ion-exchange chromatography. The site of binding of the protein and its presence in nuclei of lymphoid cells suggest that it may function in the assembly of immunoglobulin genes.

Full text

PDF
7019

Images in this article

7020Image
on p.7020
7021Image
on p.7021
7021Image
on p.7021
7022Image
on p.7022
7022Image
on p.7022

Selected References

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

  1. Alessandrini A., Pierce J. H., Baltimore D., Desiderio S. V. Continuing rearrangement of immunoglobulin and T-cell receptor genes in a Ha-ras-transformed lymphoid progenitor cell line. Proc Natl Acad Sci U S A. 1987 Apr;84(7):1799–1803. doi: 10.1073/pnas.84.7.1799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  4. Cory S., Adams J. M., Kemp D. J. Somatic rearrangements forming active immunoglobulin mu genes in B and T lymphoid cell lines. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4943–4947. doi: 10.1073/pnas.77.8.4943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis M. M. Molecular genetics of the T cell-receptor beta chain. Annu Rev Immunol. 1985;3:537–560. doi: 10.1146/annurev.iy.03.040185.002541. [DOI] [PubMed] [Google Scholar]
  6. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Feddersen R. M., Van Ness B. G. Double recombination of a single immunoglobulin kappa-chain allele: implications for the mechanism of rearrangement. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4793–4797. doi: 10.1073/pnas.82.14.4793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garner M. M., Revzin A. A gel electrophoresis method for quantifying the binding of proteins to specific DNA regions: application to components of the Escherichia coli lactose operon regulatory system. Nucleic Acids Res. 1981 Jul 10;9(13):3047–3060. doi: 10.1093/nar/9.13.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Haars R., Kronenberg M., Gallatin W. M., Weissman I. L., Owen F. L., Hood L. Rearrangement and expression of T cell antigen receptor and gamma genes during thymic development. J Exp Med. 1986 Jul 1;164(1):1–24. doi: 10.1084/jem.164.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Halligan B. D., Edwards K. A., Liu L. F. Purification and characterization of a type II DNA topoisomerase from bovine calf thymus. J Biol Chem. 1985 Feb 25;260(4):2475–2482. [PubMed] [Google Scholar]
  13. Honjo T., Habu S. Origin of immune diversity: genetic variation and selection. Annu Rev Biochem. 1985;54:803–830. doi: 10.1146/annurev.bi.54.070185.004103. [DOI] [PubMed] [Google Scholar]
  14. Kleinfield R., Hardy R. R., Tarlinton D., Dangl J., Herzenberg L. A., Weigert M. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma. 1986 Aug 28-Sep 3Nature. 322(6082):843–846. doi: 10.1038/322843a0. [DOI] [PubMed] [Google Scholar]
  15. Kurosawa Y., von Boehmer H., Haas W., Sakano H., Trauneker A., Tonegawa S. Identification of D segments of immunoglobulin heavy-chain genes and their rearrangement in T lymphocytes. Nature. 1981 Apr 16;290(5807):565–570. doi: 10.1038/290565a0. [DOI] [PubMed] [Google Scholar]
  16. Lewis S., Gifford A., Baltimore D. Joining of V kappa to J kappa gene segments in a retroviral vector introduced into lymphoid cells. 1984 Mar 29-Apr 4Nature. 308(5958):425–428. doi: 10.1038/308425a0. [DOI] [PubMed] [Google Scholar]
  17. Lewis S., Rosenberg N., Alt F., Baltimore D. Continuing kappa-gene rearrangement in a cell line transformed by Abelson murine leukemia virus. Cell. 1982 Oct;30(3):807–816. doi: 10.1016/0092-8674(82)90285-9. [DOI] [PubMed] [Google Scholar]
  18. Litman G. W., Berger L., Murphy K., Litman R., Hinds K., Erickson B. W. Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2082–2086. doi: 10.1073/pnas.82.7.2082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pelicci P. G., Knowles D. M., 2nd, Dalla Favera R. Lymphoid tumors displaying rearrangements of both immunoglobulin and T cell receptor genes. J Exp Med. 1985 Sep 1;162(3):1015–1024. doi: 10.1084/jem.162.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reth M., Gehrmann P., Petrac E., Wiese P. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. 1986 Aug 28-Sep 3Nature. 322(6082):840–842. doi: 10.1038/322840a0. [DOI] [PubMed] [Google Scholar]
  21. Rosenfeld P. J., Kelly T. J. Purification of nuclear factor I by DNA recognition site affinity chromatography. J Biol Chem. 1986 Jan 25;261(3):1398–1408. [PubMed] [Google Scholar]
  22. Rosenfeld P. J., O'Neill E. A., Wides R. J., Kelly T. J. Sequence-specific interactions between cellular DNA-binding proteins and the adenovirus origin of DNA replication. Mol Cell Biol. 1987 Feb;7(2):875–886. doi: 10.1128/mcb.7.2.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
  24. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  25. Solomon M. J., Strauss F., Varshavsky A. A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1276–1280. doi: 10.1073/pnas.83.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Strauss F., Varshavsky A. A protein binds to a satellite DNA repeat at three specific sites that would be brought into mutual proximity by DNA folding in the nucleosome. Cell. 1984 Jul;37(3):889–901. doi: 10.1016/0092-8674(84)90424-0. [DOI] [PubMed] [Google Scholar]
  27. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  28. Weaver D., Baltimore D. B lymphocyte-specific protein binding near an immunoglobulin kappa-chain gene J segment. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1516–1520. doi: 10.1073/pnas.84.6.1516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yancopoulos G. D., Blackwell T. K., Suh H., Hood L., Alt F. W. 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):251–259. doi: 10.1016/0092-8674(86)90759-2. [DOI] [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