Abstract
Previous cotransfection experiments had demonstrated that ectopic expression of the lymphocyte-specific transcription factor Oct2 could efficiently activate a promoter containing an octamer motif. Oct2 expression was unable to stimulate a multimerized octamer enhancer element in HeLa cells, however. We have tested a variety of Oct2 isoforms generated by alternative splicing for the capability to activate an octamer enhancer in nonlymphoid cells and a B-cell line. Our analyses show that several Oct2 isoforms can stimulate from a remote position but that this stimulation is restricted to B cells. This result indicates the involvement of either a B-cell-specific cofactor or a specific modification of a cofactor or the Oct2 protein in Oct2-mediated enhancer activation. Mutational analyses indicate that the carboxy-terminal domain of Oct2 is critical for enhancer activation. Moreover, this domain conferred enhancing activity when fused to the Oct1 protein, which by itself was unable to stimulate from a remote position. The glutamine-rich activation domain present in the amino-terminal portion of Oct2 and the POU domain contribute only marginally to the transactivation function from a distal position.
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- Annweiler A., Müller U., Wirth T. Functional analysis of defined mutations in the immunoglobulin heavy-chain enhancer in transgenic mice. Nucleic Acids Res. 1992 Apr 11;20(7):1503–1509. doi: 10.1093/nar/20.7.1503. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clerc R. G., Corcoran L. M., LeBowitz J. H., Baltimore D., Sharp P. A. The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev. 1988 Dec;2(12A):1570–1581. doi: 10.1101/gad.2.12a.1570. [DOI] [PubMed] [Google Scholar]
- Courey A. J., Holtzman D. A., Jackson S. P., Tjian R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell. 1989 Dec 1;59(5):827–836. doi: 10.1016/0092-8674(89)90606-5. [DOI] [PubMed] [Google Scholar]
- Currie R. A., Roeder R. G. Identification of an octamer-binding site in the mouse kappa light-chain immunoglobulin enhancer. Mol Cell Biol. 1989 Oct;9(10):4239–4247. doi: 10.1128/mcb.9.10.4239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daley G. Q., Van Etten R. A., Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990 Feb 16;247(4944):824–830. doi: 10.1126/science.2406902. [DOI] [PubMed] [Google Scholar]
- Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Falkner F. G., Zachau H. G. Correct transcription of an immunoglobulin kappa gene requires an upstream fragment containing conserved sequence elements. Nature. 1984 Jul 5;310(5972):71–74. doi: 10.1038/310071a0. [DOI] [PubMed] [Google Scholar]
- Forsberg M., Westin G. Enhancer activation by a single type of transcription factor shows cell type dependence. EMBO J. 1991 Sep;10(9):2543–2551. doi: 10.1002/j.1460-2075.1991.tb07794.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gerster T., Matthias P., Thali M., Jiricny J., Schaffner W. Cell type-specificity elements of the immunoglobulin heavy chain gene enhancer. EMBO J. 1987 May;6(5):1323–1330. doi: 10.1002/j.1460-2075.1987.tb02371.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Giri I., Yaniv M. Structural and mutational analysis of E2 trans-activating proteins of papillomaviruses reveals three distinct functional domains. EMBO J. 1988 Sep;7(9):2823–2829. doi: 10.1002/j.1460-2075.1988.tb03138.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ham J., Dostatni N., Arnos F., Yaniv M. Several different upstream promoter elements can potentiate transactivation by the BPV-1 E2 protein. EMBO J. 1991 Oct;10(10):2931–2940. doi: 10.1002/j.1460-2075.1991.tb07843.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hen R., Borrelli E., Chambon P. Repression of the immunoglobulin heavy chain enhancer by the adenovirus-2 E1A products. Science. 1985 Dec 20;230(4732):1391–1394. doi: 10.1126/science.2999984. [DOI] [PubMed] [Google Scholar]
- Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
- Hermanson G. G., Briskin M., Sigman D., Wall R. Immunoglobulin enhancer and promoter motifs 5' of the B29 B-cell-specific gene. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7341–7345. doi: 10.1073/pnas.86.19.7341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Junker S., Pedersen S., Schreiber E., Matthias P. Extinction of an immunoglobulin kappa promoter in cell hybrids is mediated by the octamer motif and correlates with suppression of Oct-2 expression. Cell. 1990 May 4;61(3):467–474. doi: 10.1016/0092-8674(90)90528-m. [DOI] [PubMed] [Google Scholar]
- Kemler I., Bucher E., Seipel K., Müller-Immerglück M. M., Schaffner W. Promoters with the octamer DNA motif (ATGCAAAT) can be ubiquitous or cell type-specific depending on binding affinity of the octamer site and Oct-factor concentration. Nucleic Acids Res. 1991 Jan 25;19(2):237–242. doi: 10.1093/nar/19.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LaBella F., Sive H. L., Roeder R. G., Heintz N. Cell-cycle regulation of a human histone H2b gene is mediated by the H2b subtype-specific consensus element. Genes Dev. 1988 Jan;2(1):32–39. doi: 10.1101/gad.2.1.32. [DOI] [PubMed] [Google Scholar]
- Landolfi N. F., Capra J. D., Tucker P. W. Interaction of cell-type-specific nuclear proteins with immunoglobulin VH promoter region sequences. Nature. 1986 Oct 9;323(6088):548–551. doi: 10.1038/323548a0. [DOI] [PubMed] [Google Scholar]
- Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
- Lewin B. Commitment and activation at pol II promoters: a tail of protein-protein interactions. Cell. 1990 Jun 29;61(7):1161–1164. doi: 10.1016/0092-8674(90)90675-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Müller M. M., Ruppert S., Schaffner W., Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. doi: 10.1038/336544a0. [DOI] [PubMed] [Google Scholar]
- Nelms K., Van Ness B. Identification of an octamer-binding site in the human kappa light-chain enhancer. Mol Cell Biol. 1990 Jul;10(7):3843–3846. doi: 10.1128/mcb.10.7.3843. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okamoto K., Okazawa H., Okuda A., Sakai M., Muramatsu M., Hamada H. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell. 1990 Feb 9;60(3):461–472. doi: 10.1016/0092-8674(90)90597-8. [DOI] [PubMed] [Google Scholar]
- Pellett P. E., McKnight J. L., Jenkins F. J., Roizman B. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870–5874. doi: 10.1073/pnas.82.17.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schatt M. D., Rusconi S., Schaffner W. A single DNA-binding transcription factor is sufficient for activation from a distant enhancer and/or from a promoter position. EMBO J. 1990 Feb;9(2):481–487. doi: 10.1002/j.1460-2075.1990.tb08134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scheidereit C., Cromlish J. A., Gerster T., Kawakami K., Balmaceda C. G., Currie R. A., Roeder R. G. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature. 1988 Dec 8;336(6199):551–557. doi: 10.1038/336551a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Sorger P. K., Pelham H. R. Yeast heat shock factor is an essential DNA-binding protein that exhibits temperature-dependent phosphorylation. Cell. 1988 Sep 9;54(6):855–864. doi: 10.1016/s0092-8674(88)91219-6. [DOI] [PubMed] [Google Scholar]
- Staudt L. M., Clerc R. G., Singh H., LeBowitz J. H., Sharp P. A., Baltimore D. Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science. 1988 Jul 29;241(4865):577–580. doi: 10.1126/science.3399892. [DOI] [PubMed] [Google Scholar]
- Staudt L. M., Singh H., Sen R., Wirth T., Sharp P. A., Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature. 1986 Oct 16;323(6089):640–643. doi: 10.1038/323640a0. [DOI] [PubMed] [Google Scholar]
- Stern S., Tanaka M., Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. doi: 10.1038/341624a0. [DOI] [PubMed] [Google Scholar]
- Sterneck E., Müller C., Katz S., Leutz A. Autocrine growth induced by kinase type oncogenes in myeloid cells requires AP-1 and NF-M, a myeloid specific, C/EBP-like factor. EMBO J. 1992 Jan;11(1):115–126. doi: 10.1002/j.1460-2075.1992.tb05034.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturm R. A., Das G., Herr W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988 Dec;2(12A):1582–1599. doi: 10.1101/gad.2.12a.1582. [DOI] [PubMed] [Google Scholar]
- Suzuki N., Rohdewohld H., Neuman T., Gruss P., Schöler H. R. Oct-6: a POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 1990 Nov;9(11):3723–3732. doi: 10.1002/j.1460-2075.1990.tb07585.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tanaka M., Lai J. S., Herr W. Promoter-selective activation domains in Oct-1 and Oct-2 direct differential activation of an snRNA and mRNA promoter. Cell. 1992 Feb 21;68(4):755–767. doi: 10.1016/0092-8674(92)90150-b. [DOI] [PubMed] [Google Scholar]
- Wirth T., Baltimore D. Nuclear factor NF-kappa B can interact functionally with its cognate binding site to provide lymphoid-specific promoter function. EMBO J. 1988 Oct;7(10):3109–3113. doi: 10.1002/j.1460-2075.1988.tb03177.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wirth T., Priess A., Annweiler A., Zwilling S., Oeler B. Multiple Oct2 isoforms are generated by alternative splicing. Nucleic Acids Res. 1991 Jan 11;19(1):43–51. doi: 10.1093/nar/19.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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. doi: 10.1038/329174a0. [DOI] [PubMed] [Google Scholar]
- Yamamoto K. K., Gonzalez G. A., Biggs W. H., 3rd, Montminy M. R. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature. 1988 Aug 11;334(6182):494–498. doi: 10.1038/334494a0. [DOI] [PubMed] [Google Scholar]
- Yu H., Porton B., Shen L. Y., Eckhardt L. A. Role of the octamer motif in hybrid cell extinction of immunoglobulin gene expression: extinction is dominant in a two enhancer system. Cell. 1989 Aug 11;58(3):441–448. doi: 10.1016/0092-8674(89)90425-x. [DOI] [PubMed] [Google Scholar]
- de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]