Abstract
During intrathymic differentiation, the genes coding for the T cell receptor/CD3 (TCR/CD3) complex are expressed in stages resulting in surface expression of competent receptors on the most mature T cells. The CD3-delta, gamma and epsilon proteins, which are expressed intracellularly in the earliest detectable cells of T lineage, form the core of the TCR/CD3 complex. In the present investigation aimed at understanding the tissue specific expression of the murine CD3-delta gene, a T cell specific DNase I hypersensitive site was found 0.6 kb downstream of the polyadenylation site of the gene. A 0.4 kb genomic fragment encompassing this hypersensitive site exhibited properties of a strictly T cell-specific transcriptional enhancer which acts in a position- and orientation-independent manner. However, the activity of the promoter region was not found to be T cell restricted. Within this novel T cell-specific enhancer region, sequence motifs were found which are shared with the promoters of both the mouse and human CD3-delta genes; in this region we also found sequence homologies to the enhancer core element of the thymotropic viruses SL3 and RadLV. These findings suggest that regulatory elements 3' of the CD3-delta gene are at least in part responsible for its exclusive expression in thymus-derived lymphocytes.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alarcon B., Berkhout B., Breitmeyer J., Terhorst C. Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma.delta.epsilon core and single T cell receptor alpha or beta chains. J Biol Chem. 1988 Feb 25;263(6):2953–2961. [PubMed] [Google Scholar]
- Angel P., Imagawa M., Chiu R., Stein B., Imbra R. J., Rahmsdorf H. J., Jonat C., Herrlich P., Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor. Cell. 1987 Jun 19;49(6):729–739. doi: 10.1016/0092-8674(87)90611-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Becker P., Renkawitz R., Schütz G. Tissue-specific DNaseI hypersensitive sites in the 5'-flanking sequences of the tryptophan oxygenase and the tyrosine aminotransferase genes. EMBO J. 1984 Sep;3(9):2015–2020. doi: 10.1002/j.1460-2075.1984.tb02084.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bier E., Hashimoto Y., Greene M. I., Maxam A. M. Active T-cell receptor genes have intron deoxyribonuclease hypersensitive sites. Science. 1985 Aug 9;229(4713):528–534. doi: 10.1126/science.3927483. [DOI] [PubMed] [Google Scholar]
- Borst J., Prendiville M. A., Terhorst C. Complexity of the human T lymphocyte-specific cell surface antigen T3. J Immunol. 1982 Apr;128(4):1560–1565. [PubMed] [Google Scholar]
- Celander D., Haseltine W. A. Glucocorticoid regulation of murine leukemia virus transcription elements is specified by determinants within the viral enhancer region. J Virol. 1987 Feb;61(2):269–275. doi: 10.1128/jvi.61.2.269-275.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chandler V. L., Maler B. A., Yamamoto K. R. DNA sequences bound specifically by glucocorticoid receptor in vitro render a heterologous promoter hormone responsive in vivo. Cell. 1983 Jun;33(2):489–499. doi: 10.1016/0092-8674(83)90430-0. [DOI] [PubMed] [Google Scholar]
- Church G. M., Ephrussi A., Gilbert W., Tonegawa S. Cell-type-specific contacts to immunoglobulin enhancers in nuclei. 1985 Feb 28-Mar 6Nature. 313(6005):798–801. doi: 10.1038/313798a0. [DOI] [PubMed] [Google Scholar]
- Davey M. P., Bongiovanni K. F., Kaulfersch W., Quertermous T., Seidman J. G., Hershfield M. S., Kurtzberg J., Haynes B. F., Davis M. M., Waldmann T. A. Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8759–8763. doi: 10.1073/pnas.83.22.8759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DeFranco D., Yamamoto K. R. Two different factors act separately or together to specify functionally distinct activities at a single transcriptional enhancer. Mol Cell Biol. 1986 Apr;6(4):993–1001. doi: 10.1128/mcb.6.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
- Ephrussi A., Church G. M., Tonegawa S., Gilbert W. B lineage--specific interactions of an immunoglobulin enhancer with cellular factors in vivo. Science. 1985 Jan 11;227(4683):134–140. doi: 10.1126/science.3917574. [DOI] [PubMed] [Google Scholar]
- Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
- Furley A. J., Mizutani S., Weilbaecher K., Dhaliwal H. S., Ford A. M., Chan L. C., Molgaard H. V., Toyonaga B., Mak T., van den Elsen P. Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. Cell. 1986 Jul 4;46(1):75–87. doi: 10.1016/0092-8674(86)90861-5. [DOI] [PubMed] [Google Scholar]
- Garcia J. V., Bich-Thuy L. T., Stafford J., Queen C. Synergism between immunoglobulin enhancers and promoters. Nature. 1986 Jul 24;322(6077):383–385. doi: 10.1038/322383a0. [DOI] [PubMed] [Google Scholar]
- Gillies S. D., Folsom V., Tonegawa S. Cell type-specific enhancer element associated with a mouse MHC gene, E beta. Nature. 1984 Aug 16;310(5978):594–597. doi: 10.1038/310594a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
- Graves B. J., Eisenman R. N., McKnight S. L. Delineation of transcriptional control signals within the Moloney murine sarcoma virus long terminal repeat. Mol Cell Biol. 1985 Aug;5(8):1948–1958. doi: 10.1128/mcb.5.8.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
- Jantzen H. M., Strähle U., Gloss B., Stewart F., Schmid W., Boshart M., Miksicek R., Schütz G. Cooperativity of glucocorticoid response elements located far upstream of the tyrosine aminotransferase gene. Cell. 1987 Apr 10;49(1):29–38. doi: 10.1016/0092-8674(87)90752-5. [DOI] [PubMed] [Google Scholar]
- Kemper B., Jackson P. D., Felsenfeld G. Protein-binding sites within the 5' DNase I-hypersensitive region of the chicken alpha D-globin gene. Mol Cell Biol. 1987 Jun;7(6):2059–2069. doi: 10.1128/mcb.7.6.2059. [DOI] [PMC free article] [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]
- Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
- Luria S., Gross G., Horowitz M., Givol D. Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor. EMBO J. 1987 Nov;6(11):3307–3312. doi: 10.1002/j.1460-2075.1987.tb02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McGhee J. D., Wood W. I., Dolan M., Engel J. D., Felsenfeld G. A 200 base pair region at the 5' end of the chicken adult beta-globin gene is accessible to nuclease digestion. Cell. 1981 Nov;27(1 Pt 2):45–55. doi: 10.1016/0092-8674(81)90359-7. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Acuto O., Hussey R. E., Hodgdon J. C., Fitzgerald K. A., Schlossman S. F., Reinherz E. L. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor. Nature. 1983 Jun 30;303(5920):808–810. doi: 10.1038/303808a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
- Ptashne M. Gene regulation by proteins acting nearby and at a distance. Nature. 1986 Aug 21;322(6081):697–701. doi: 10.1038/322697a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Queen C., Stafford J. Fine mapping of an immunoglobulin gene activator. Mol Cell Biol. 1984 Jun;4(6):1042–1049. doi: 10.1128/mcb.4.6.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rassart E., Shang M., Boie Y., Jolicoeur P. Studies on emerging radiation leukemia virus variants in C57BL/Ka mice. J Virol. 1986 Apr;58(1):96–106. doi: 10.1128/jvi.58.1.96-106.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saito H., Koyama T., Georgopoulos K., Clevers H., Haser W. G., LeBien T., Tonegawa S., Terhorst C. Close linkage of the mouse and human CD3 gamma- and delta-chain genes suggests that their transcription is controlled by common regulatory elements. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9131–9134. doi: 10.1073/pnas.84.24.9131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schöler H. R., Gruss P. Specific interaction between enhancer-containing molecules and cellular components. Cell. 1984 Feb;36(2):403–411. doi: 10.1016/0092-8674(84)90233-2. [DOI] [PubMed] [Google Scholar]
- Shackelford D. A., Smith A. V., Trowbridge I. S. Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor. J Immunol. 1987 Jan 15;138(2):613–619. [PubMed] [Google Scholar]
- 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]
- Stalder J., Groudine M., Dodgson J. B., Engel J. D., Weintraub H. Hb switching in chickens. Cell. 1980 Apr;19(4):973–980. doi: 10.1016/0092-8674(80)90088-4. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Vigneron M., Matthes H., Wildeman A., Zenke M., Chambon P. Requirement of stereospecific alignments for initiation from the simian virus 40 early promoter. Nature. 1986 Jan 9;319(6049):121–126. doi: 10.1038/319121a0. [DOI] [PubMed] [Google Scholar]
- Treisman R., Green M. R., Maniatis T. cis and trans activation of globin gene transcription in transient assays. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7428–7432. doi: 10.1073/pnas.80.24.7428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tunnacliffe A., Buluwela L., Rabbitts T. H. Physical linkage of three CD3 genes on human chromosome 11. EMBO J. 1987 Oct;6(10):2953–2957. doi: 10.1002/j.1460-2075.1987.tb02600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
- Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Dongen J. J., Quertermous T., Bartram C. R., Gold D. P., Wolvers-Tettero I. L., Comans-Bitter W. M., Hooijkaas H., Adriaansen H. J., de Klein A., Raghavachar A. T cell receptor-CD3 complex during early T cell differentiation. Analysis of immature T cell acute lymphoblastic leukemias (T-ALL) at DNA, RNA, and cell membrane level. J Immunol. 1987 Feb 15;138(4):1260–1269. [PubMed] [Google Scholar]
- van den Elsen P., Georgopoulos K., Shepley B. A., Orkin S., Terhorst C. Exon/intron organization of the genes coding for the delta chains of the human and murine T-cell receptor/T3 complex. Proc Natl Acad Sci U S A. 1986 May;83(9):2944–2948. doi: 10.1073/pnas.83.9.2944. [DOI] [PMC free article] [PubMed] [Google Scholar]