Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Aug;15(8):4115–4124. doi: 10.1128/mcb.15.8.4115

Cloning, functional characterization, and mechanism of action of the B-cell-specific transcriptional coactivator OCA-B.

Y Luo 1, R G Roeder 1
PMCID: PMC230650  PMID: 7623806

Abstract

Biochemical purification and cognate cDNA cloning studies have revealed that the previously described transcriptional coactivator OCA-B consists of a 34- or 35-kDa polypeptide with sequence relationships to known coactivators that function by protein-protein interactions. Studies with a recombinant protein have proved that a single OCA-B polypeptide is the main determinant for B-cell-specific activation of immunoglobulin (Ig) promoters and provided additional insights into its mechanism of action. Recombinant OCA-B can function equally well with Oct-1 or Oct-2 on an Ig promoter, but while corresponding POU domains are sufficient for OCA-B interaction, and for octamer-mediated transcription of a histone H2B promoter, an additional Oct-1 or Oct-2 activation domain(s) is necessary for functional synergy with OCA-B. Further studies additional Oct-1 or Oct-2 activation domain(s) is necessary for functional synergy with OCA-B. Further studies show that Ig promoter activation by Oct-1 and OCA-B requires still other general (USA-derived) cofactors and also provide indirect evidence that distinct Oct-interacting cofactors regulate H2B transcription.

Full Text

The Full Text of this article is available as a PDF (572.7 KB).

Selected References

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

  1. Alt F. W., Blackwell T. K., Yancopoulos G. D. Development of the primary antibody repertoire. Science. 1987 Nov 20;238(4830):1079–1087. doi: 10.1126/science.3317825. [DOI] [PubMed] [Google Scholar]
  2. Annweiler A., Müller-Immerglück M., Wirth T. Oct2 transactivation from a remote enhancer position requires a B-cell-restricted activity. Mol Cell Biol. 1992 Jul;12(7):3107–3116. doi: 10.1128/mcb.12.7.3107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cleary M. A., Stern S., Tanaka M., Herr W. Differential positive control by Oct-1 and Oct-2: activation of a transcriptionally silent motif through Oct-1 and VP16 corecruitment. Genes Dev. 1993 Jan;7(1):72–83. doi: 10.1101/gad.7.1.72. [DOI] [PubMed] [Google Scholar]
  4. Corcoran L. M., Karvelas M., Nossal G. J., Ye Z. S., Jacks T., Baltimore D. Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival. Genes Dev. 1993 Apr;7(4):570–582. doi: 10.1101/gad.7.4.570. [DOI] [PubMed] [Google Scholar]
  5. Corcoran L. M., Karvelas M. Oct-2 is required early in T cell-independent B cell activation for G1 progression and for proliferation. Immunity. 1994 Nov;1(8):635–645. doi: 10.1016/1074-7613(94)90035-3. [DOI] [PubMed] [Google Scholar]
  6. Feldhaus A. L., Klug C. A., Arvin K. L., Singh H. Targeted disruption of the Oct-2 locus in a B cell provides genetic evidence for two distinct cell type-specific pathways of octamer element-mediated gene activation. EMBO J. 1993 Jul;12(7):2763–2772. doi: 10.1002/j.1460-2075.1993.tb05937.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ge H., Roeder R. G. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell. 1994 Aug 12;78(3):513–523. doi: 10.1016/0092-8674(94)90428-6. [DOI] [PubMed] [Google Scholar]
  8. Gerster T., Balmaceda C. G., Roeder R. G. The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. EMBO J. 1990 May;9(5):1635–1643. doi: 10.1002/j.1460-2075.1990.tb08283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hayashi S., Scott M. P. What determines the specificity of action of Drosophila homeodomain proteins? Cell. 1990 Nov 30;63(5):883–894. doi: 10.1016/0092-8674(90)90492-w. [DOI] [PubMed] [Google Scholar]
  10. Helin K., Lees J. A., Vidal M., Dyson N., Harlow E., Fattaey A. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell. 1992 Jul 24;70(2):337–350. doi: 10.1016/0092-8674(92)90107-n. [DOI] [PubMed] [Google Scholar]
  11. Herr W., Sturm R. A., Clerc R. G., Corcoran L. M., Baltimore D., Sharp P. A., Ingraham H. A., Rosenfeld M. G., Finney M., Ruvkun G. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988 Dec;2(12A):1513–1516. doi: 10.1101/gad.2.12a.1513. [DOI] [PubMed] [Google Scholar]
  12. Himmelfarb H. J., Pearlberg J., Last D. H., Ptashne M. GAL11P: a yeast mutation that potentiates the effect of weak GAL4-derived activators. Cell. 1990 Dec 21;63(6):1299–1309. doi: 10.1016/0092-8674(90)90425-e. [DOI] [PubMed] [Google Scholar]
  13. Kretzschmar M., Kaiser K., Lottspeich F., Meisterernst M. A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell. 1994 Aug 12;78(3):525–534. doi: 10.1016/0092-8674(94)90429-4. [DOI] [PubMed] [Google Scholar]
  14. Kwok R. P., Lundblad J. R., Chrivia J. C., Richards J. P., Bächinger H. P., Brennan R. G., Roberts S. G., Green M. R., Goodman R. H. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994 Jul 21;370(6486):223–226. doi: 10.1038/370223a0. [DOI] [PubMed] [Google Scholar]
  15. Laurent B. C., Treitel M. A., Carlson M. The SNF5 protein of Saccharomyces cerevisiae is a glutamine- and proline-rich transcriptional activator that affects expression of a broad spectrum of genes. Mol Cell Biol. 1990 Nov;10(11):5616–5625. doi: 10.1128/mcb.10.11.5616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ling P. D., Ryon J. J., Hayward S. D. EBNA-2 of herpesvirus papio diverges significantly from the type A and type B EBNA-2 proteins of Epstein-Barr virus but retains an efficient transactivation domain with a conserved hydrophobic motif. J Virol. 1993 Jun;67(6):2990–3003. doi: 10.1128/jvi.67.6.2990-3003.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Liu F., Green M. R. Promoter targeting by adenovirus E1a through interaction with different cellular DNA-binding domains. Nature. 1994 Apr 7;368(6471):520–525. doi: 10.1038/368520a0. [DOI] [PubMed] [Google Scholar]
  18. Luo Y., Fujii H., Gerster T., Roeder R. G. A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors. Cell. 1992 Oct 16;71(2):231–241. doi: 10.1016/0092-8674(92)90352-d. [DOI] [PubMed] [Google Scholar]
  19. Meisterernst M., Roy A. L., Lieu H. M., Roeder R. G. Activation of class II gene transcription by regulatory factors is potentiated by a novel activity. Cell. 1991 Sep 6;66(5):981–993. doi: 10.1016/0092-8674(91)90443-3. [DOI] [PubMed] [Google Scholar]
  20. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  21. Murphy S., Yoon J. B., Gerster T., Roeder R. G. Oct-1 and Oct-2 potentiate functional interactions of a transcription factor with the proximal sequence element of small nuclear RNA genes. Mol Cell Biol. 1992 Jul;12(7):3247–3261. doi: 10.1128/mcb.12.7.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mylin L. M., Gerardot C. J., Hopper J. E., Dickson R. C. Sequence conservation in the Saccharomyces and Kluveromyces GAL11 transcription activators suggests functional domains. Nucleic Acids Res. 1991 Oct 11;19(19):5345–5350. doi: 10.1093/nar/19.19.5345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Müller-Immerglück M. M., Schaffner W., Matthias P. Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J. 1990 May;9(5):1625–1634. doi: 10.1002/j.1460-2075.1990.tb08282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pierani A., Heguy A., Fujii H., Roeder R. G. Activation of octamer-containing promoters by either octamer-binding transcription factor 1 (OTF-1) or OTF-2 and requirement of an additional B-cell-specific component for optimal transcription of immunoglobulin promoters. Mol Cell Biol. 1990 Dec;10(12):6204–6215. doi: 10.1128/mcb.10.12.6204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pomerantz J. L., Kristie T. M., Sharp P. A. Recognition of the surface of a homeo domain protein. Genes Dev. 1992 Nov;6(11):2047–2057. doi: 10.1101/gad.6.11.2047. [DOI] [PubMed] [Google Scholar]
  26. Qin X. F., Luo Y., Suh H., Wayne J., Misulovin Z., Roeder R. G., Nussenzweig M. C. Transformation by homeobox genes can be mediated by selective transcriptional repression. EMBO J. 1994 Dec 15;13(24):5967–5976. doi: 10.1002/j.1460-2075.1994.tb06942.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Radomska H. S., Shen C. P., Kadesch T., Eckhardt L. A. Constitutively expressed Oct-2 prevents immunoglobulin gene silencing in myeloma x T cell hybrids. Immunity. 1994 Nov;1(8):623–634. doi: 10.1016/1074-7613(94)90034-5. [DOI] [PubMed] [Google Scholar]
  28. Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
  29. Ruvkun G., Finney M. Regulation of transcription and cell identity by POU domain proteins. Cell. 1991 Feb 8;64(3):475–478. doi: 10.1016/0092-8674(91)90227-p. [DOI] [PubMed] [Google Scholar]
  30. Schöler H. R., Ciesiolka T., Gruss P. A nexus between Oct-4 and E1A: implications for gene regulation in embryonic stem cells. Cell. 1991 Jul 26;66(2):291–304. doi: 10.1016/0092-8674(91)90619-a. [DOI] [PubMed] [Google Scholar]
  31. Schöler H. R. Octamania: the POU factors in murine development. Trends Genet. 1991 Oct;7(10):323–329. doi: 10.1016/0168-9525(91)90422-m. [DOI] [PubMed] [Google Scholar]
  32. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  33. Staudt L. M., Lenardo M. J. Immunoglobulin gene transcription. Annu Rev Immunol. 1991;9:373–398. doi: 10.1146/annurev.iy.09.040191.002105. [DOI] [PubMed] [Google Scholar]
  34. Swaffield J. C., Melcher K., Johnston S. A. A highly conserved ATPase protein as a mediator between acidic activation domains and the TATA-binding protein. Nature. 1995 Mar 2;374(6517):88–91. doi: 10.1038/374088a0. [DOI] [PubMed] [Google Scholar]
  35. Tanaka M., Herr W. Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell. 1990 Feb 9;60(3):375–386. doi: 10.1016/0092-8674(90)90589-7. [DOI] [PubMed] [Google Scholar]
  36. Walker S., Hayes S., O'Hare P. Site-specific conformational alteration of the Oct-1 POU domain-DNA complex as the basis for differential recognition by Vmw65 (VP16). Cell. 1994 Dec 2;79(5):841–852. doi: 10.1016/0092-8674(94)90073-6. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES