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. 1993 Mar 25;21(6):1481–1488. doi: 10.1093/nar/21.6.1481

Regulatory elements necessary for termination of transcription within the Ig heavy chain gene locus.

B B Moore 1, J Tan 1, P L Lim 1, P W Tucker 1, D Yuan 1
PMCID: PMC309336  PMID: 8464741

Abstract

Previous experiments have shown that the extent of delta gene transcription during B cell development is regulated primarily at the transcriptional level. We have shown that deletion of a sequence located between the mu and delta coding regions in the Ig heavy chain locus where transcriptional termination has been previously mapped abrogates the termination. Restoration of termination requires reintroduction of this segment as well as sequence elements within the microM poly (A) site which cannot be substituted by the microS poly (A) site. Recognition of the termination site by non-lymphoid cells suggests that initiation of delta transcription in mature B lymphocytes requires the activation of an anti-termination mechanism not yet developed in early B cells.

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Selected References

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  1. Alt F. W., Rosenberg N., Enea V., Siden E., Baltimore D. Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines. Mol Cell Biol. 1982 Apr;2(4):386–400. doi: 10.1128/mcb.2.4.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bentley D. L., Groudine M. Sequence requirements for premature termination of transcription in the human c-myc gene. Cell. 1988 Apr 22;53(2):245–256. doi: 10.1016/0092-8674(88)90386-8. [DOI] [PubMed] [Google Scholar]
  3. Burrows P. D., Beck-Engeser G. B., Wabl M. R. Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement. Nature. 1983 Nov 17;306(5940):243–246. doi: 10.1038/306243a0. [DOI] [PubMed] [Google Scholar]
  4. Chen-Bettecken U., Wecker E., Schimpl A. IgM RNA switch from membrane to secretory form is prevented by adding antireceptor antibody to bacterial lipopolysaccharide-stimulated murine primary B-cell cultures. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7384–7388. doi: 10.1073/pnas.82.21.7384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cheng H. L., Blattner F. R., Fitzmaurice L., Mushinski J. F., Tucker P. W. Structure of genes for membrane and secreted murine IgD heavy chains. Nature. 1982 Apr 1;296(5856):410–415. doi: 10.1038/296410a0. [DOI] [PubMed] [Google Scholar]
  6. Falck-Pedersen E., Logan J., Shenk T., Darnell J. E., Jr Transcription termination within the E1A gene of adenovirus induced by insertion of the mouse beta-major globin terminator element. Cell. 1985 Apr;40(4):897–905. doi: 10.1016/0092-8674(85)90349-6. [DOI] [PubMed] [Google Scholar]
  7. Galli G., Guise J. W., McDevitt M. A., Tucker P. W., Nevins J. R. Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development. Genes Dev. 1987 Jul;1(5):471–481. doi: 10.1101/gad.1.5.471. [DOI] [PubMed] [Google Scholar]
  8. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  9. Guise J. W., Lim P. L., Yuan D., Tucker P. W. Alternative expression of secreted and membrane forms of immunoglobulin mu-chain is regulated by transcriptional termination in stable plasmacytoma transfectants. J Immunol. 1988 Jun 1;140(11):3988–3994. [PubMed] [Google Scholar]
  10. Honjo T. Immunoglobulin genes. Annu Rev Immunol. 1983;1:499–528. doi: 10.1146/annurev.iy.01.040183.002435. [DOI] [PubMed] [Google Scholar]
  11. Kelley D. E., Perry R. P. Transcriptional and posttranscriptional control of immunoglobulin mRNA production during B lymphocyte development. Nucleic Acids Res. 1986 Jul 11;14(13):5431–5447. doi: 10.1093/nar/14.13.5431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knapp M. R., Liu C. P., Newell N., Ward R. B., Tucker P. W., Strober S., Blattner F. Simultaneous expression of immunoglobulin mu and delta heavy chains by a cloned B-cell lymphoma: a single copy of the VH gene is shared by two adjacent CH genes. Proc Natl Acad Sci U S A. 1982 May;79(9):2996–3000. doi: 10.1073/pnas.79.9.2996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Laskov R., Kim J. K., Woods V. L., McKeever P. E., Asofsky R. Membrane immunoglobulins of spontaneous B lymphomas of aged BALB/c mice. Eur J Immunol. 1981 Jun;11(6):462–468. doi: 10.1002/eji.1830110605. [DOI] [PubMed] [Google Scholar]
  14. Law R., Kuwabara M. D., Briskin M., Fasel N., Hermanson G., Sigman D. S., Wall R. Protein-binding site at the immunoglobulin mu membrane polyadenylylation signal: possible role in transcription termination. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9160–9164. doi: 10.1073/pnas.84.24.9160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Leanderson T., Hsu E. Anti-IgM treatment influences immunoglobulin heavy and light chain mRNA levels in mitogen-stimulated B lymphocytes. Eur J Immunol. 1985 Jun;15(6):641–643. doi: 10.1002/eji.1830150621. [DOI] [PubMed] [Google Scholar]
  16. Liu C. P., Tucker P. W., Mushinski J. F., Blattner F. R. Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980 Sep 19;209(4463):1348–1353. doi: 10.1126/science.6774414. [DOI] [PubMed] [Google Scholar]
  17. Logan J., Falck-Pedersen E., Darnell J. E., Jr, Shenk T. A poly(A) addition site and a downstream termination region are required for efficient cessation of transcription by RNA polymerase II in the mouse beta maj-globin gene. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8306–8310. doi: 10.1073/pnas.84.23.8306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maki R., Roeder W., Traunecker A., Sidman C., Wabl M., Raschke W., Tonegawa S. The role of DNA rearrangement and alternative RNA processing in the expression of immunoglobulin delta genes. Cell. 1981 May;24(2):353–365. doi: 10.1016/0092-8674(81)90325-1. [DOI] [PubMed] [Google Scholar]
  19. Mulligan R. C., Berg P. Expression of a bacterial gene in mammalian cells. Science. 1980 Sep 19;209(4463):1422–1427. doi: 10.1126/science.6251549. [DOI] [PubMed] [Google Scholar]
  20. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Peterson M. L., Perry R. P. Regulated production of mu m and mu s mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the mu s-mu m intron. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8883–8887. doi: 10.1073/pnas.83.23.8883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pfeiffer P., Hay N., Pruzan R., Jakobovits E. B., Aloni Y. In vitro premature termination in SV40 late transcription. EMBO J. 1983;2(2):185–191. doi: 10.1002/j.1460-2075.1983.tb01403.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Raschke W. C., Baird S., Ralph P., Nakoinz I. Functional macrophage cell lines transformed by Abelson leukemia virus. Cell. 1978 Sep;15(1):261–267. doi: 10.1016/0092-8674(78)90101-0. [DOI] [PubMed] [Google Scholar]
  24. Selby M. J., Bain E. S., Luciw P. A., Peterlin B. M. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989 Apr;3(4):547–558. doi: 10.1101/gad.3.4.547. [DOI] [PubMed] [Google Scholar]
  25. Sherman P. A., Basta P. V., Heguy A., Wloch M. K., Roeder R. G., Ting J. P. The octamer motif is a B-lymphocyte-specific regulatory element of the HLA-DR alpha gene promoter. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6739–6743. doi: 10.1073/pnas.86.17.6739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tisch R., Kondo N., Hozumi N. Parameters that govern the regulation of immunoglobulin delta heavy-chain gene expression. Mol Cell Biol. 1990 Oct;10(10):5340–5348. doi: 10.1128/mcb.10.10.5340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tsurushita N., Korn L. J. Effects of intron length on differential processing of mouse mu heavy-chain mRNA. Mol Cell Biol. 1987 Jul;7(7):2602–2605. doi: 10.1128/mcb.7.7.2602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weiss E. A., Michael A., Yuan D. Role of transcriptional termination in the regulation of mu mRNA expression in B lymphocytes. J Immunol. 1989 Aug 1;143(3):1046–1052. [PubMed] [Google Scholar]
  29. Yuan D., Gilliam A. C., Tucker P. W. Regulation of expression of immunoglobulins M and D in murine B cells. Fed Proc. 1985 Jul;44(10):2652–2659. [PubMed] [Google Scholar]
  30. Yuan D., Tucker P. W. Transcriptional regulation of the mu-delta heavy chain locus in normal murine B lymphocytes. J Exp Med. 1984 Aug 1;160(2):564–583. doi: 10.1084/jem.160.2.564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yuan D., Witte P. L. Transcriptional regulation of mu and delta gene expression in bone marrow pre-B and B lymphocytes. J Immunol. 1988 Apr 15;140(8):2808–2814. [PubMed] [Google Scholar]

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