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. 1995 Mar;15(3):1662–1670. doi: 10.1128/mcb.15.3.1662

Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development.

M Satake 1, S Nomura 1, Y Yamaguchi-Iwai 1, Y Takahama 1, Y Hashimoto 1, M Niki 1, Y Kitamura 1, Y Ito 1
PMCID: PMC230390  PMID: 7862157

Abstract

The PEBP2 alpha A and PEBP2 alpha B genes encode the DNA-binding subunit of a murine transcription factor, PEBP2, which is implicated as a T-cell-specific transcriptional regulator. These two related genes share the evolutionarily conserved region encoding the Runt domain. PEBP2 alpha B is the murine counterpart of human AML1, which is located at the breakpoints of the 8;21 and 3;21 chromosome translocations associated with acute myeloid leukemia. Northern (RNA) blots of various adult mouse tissues revealed that the levels of expression of both genes were most prominent in the thymus. Furthermore, transcripts of PEBP2 alpha A and mouse AML1/PEBP2 alpha B were detected in T lymphocytes in the thymuses from day 16 embryos and newborns, as well as 4-week-old adult mice, by in situ hybridization. The expression of the genes persisted in peripheral lymph nodes of adult mice. The transcripts were detected in all the CD4- CD8-, CD4+ CD8+, CD4+ CD8-, and CD4- CD8+ cell populations. The results indicated that both genes are expressed in T cells throughout their development, supporting the notion that PEBP2 is a T-cell-specific transcription factor. Transcripts of mouse AML1/PEBP2 alpha B were also detected in day 12 fetal hematopoietic liver and in the bone marrow cells of newborn mice. The implication of mouse AML1/PEBP2 alpha B expression in hematopoietic cells other than those of T-cell lineage is discussed in relation to myeloid leukemogenesis.

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Selected References

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  1. Bae S. C., Ogawa E., Maruyama M., Oka H., Satake M., Shigesada K., Jenkins N. A., Gilbert D. J., Copeland N. G., Ito Y. PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials. Mol Cell Biol. 1994 May;14(5):3242–3252. doi: 10.1128/mcb.14.5.3242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bae S. C., Yamaguchi-Iwai Y., Ogawa E., Maruyama M., Inuzuka M., Kagoshima H., Shigesada K., Satake M., Ito Y. Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. Oncogene. 1993 Mar;8(3):809–814. [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Erickson P., Gao J., Chang K. S., Look T., Whisenant E., Raimondi S., Lasher R., Trujillo J., Rowley J., Drabkin H. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood. 1992 Oct 1;80(7):1825–1831. [PubMed] [Google Scholar]
  5. Furukawa K., Yamaguchi Y., Ogawa E., Shigesada K., Satake M., Ito Y. A ubiquitous repressor interacting with an F9 cell-specific silencer and its functional suppression by differentiated cell-specific positive factors. Cell Growth Differ. 1990 Mar;1(3):135–147. [PubMed] [Google Scholar]
  6. Georgopoulos K., Moore D. D., Derfler B. Ikaros, an early lymphoid-specific transcription factor and a putative mediator for T cell commitment. Science. 1992 Oct 30;258(5083):808–812. doi: 10.1126/science.1439790. [DOI] [PubMed] [Google Scholar]
  7. Giese K., Grosschedl R. LEF-1 contains an activation domain that stimulates transcription only in a specific context of factor-binding sites. EMBO J. 1993 Dec;12(12):4667–4676. doi: 10.1002/j.1460-2075.1993.tb06155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gottschalk L. R., Leiden J. M. Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes. Mol Cell Biol. 1990 Oct;10(10):5486–5495. doi: 10.1128/mcb.10.10.5486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hallberg B., Schmidt J., Luz A., Pedersen F. S., Grundström T. SL3-3 enhancer factor 1 transcriptional activators are required for tumor formation by SL3-3 murine leukemia virus. J Virol. 1991 Aug;65(8):4177–4181. doi: 10.1128/jvi.65.8.4177-4181.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hernandez-Munain C., Krangel M. S. Regulation of the T-cell receptor delta enhancer by functional cooperation between c-Myb and core-binding factors. Mol Cell Biol. 1994 Jan;14(1):473–483. doi: 10.1128/mcb.14.1.473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ho I. C., Bhat N. K., Gottschalk L. R., Lindsten T., Thompson C. B., Papas T. S., Leiden J. M. Sequence-specific binding of human Ets-1 to the T cell receptor alpha gene enhancer. Science. 1990 Nov 9;250(4982):814–818. doi: 10.1126/science.2237431. [DOI] [PubMed] [Google Scholar]
  12. Ho I. C., Vorhees P., Marin N., Oakley B. K., Tsai S. F., Orkin S. H., Leiden J. M. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. EMBO J. 1991 May;10(5):1187–1192. doi: 10.1002/j.1460-2075.1991.tb08059.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Houlden B. A., Cron R. Q., Coligan J. E., Bluestone J. A. Systematic development of distinct T cell receptor-gamma delta T cell subsets during fetal ontogeny. J Immunol. 1988 Dec 1;141(11):3753–3759. [PubMed] [Google Scholar]
  14. Ikuta K., Kina T., MacNeil I., Uchida N., Peault B., Chien Y. H., Weissman I. L. A developmental switch in thymic lymphocyte maturation potential occurs at the level of hematopoietic stem cells. Cell. 1990 Sep 7;62(5):863–874. doi: 10.1016/0092-8674(90)90262-d. [DOI] [PubMed] [Google Scholar]
  15. Ito K., Bonneville M., Takagaki Y., Nakanishi N., Kanagawa O., Krecko E. G., Tonegawa S. Different gamma delta T-cell receptors are expressed on thymocytes at different stages of development. Proc Natl Acad Sci U S A. 1989 Jan;86(2):631–635. doi: 10.1073/pnas.86.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Joulin V., Bories D., Eléouet J. F., Labastie M. C., Chrétien S., Mattéi M. G., Roméo P. H. A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. EMBO J. 1991 Jul;10(7):1809–1816. doi: 10.1002/j.1460-2075.1991.tb07706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kagoshima H., Shigesada K., Satake M., Ito Y., Miyoshi H., Ohki M., Pepling M., Gergen P. The Runt domain identifies a new family of heteromeric transcriptional regulators. Trends Genet. 1993 Oct;9(10):338–341. doi: 10.1016/0168-9525(93)90026-e. [DOI] [PubMed] [Google Scholar]
  18. Kamachi Y., Ogawa E., Asano M., Ishida S., Murakami Y., Satake M., Ito Y., Shigesada K. Purification of a mouse nuclear factor that binds to both the A and B cores of the polyomavirus enhancer. J Virol. 1990 Oct;64(10):4808–4819. doi: 10.1128/jvi.64.10.4808-4819.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kania M. A., Bonner A. S., Duffy J. B., Gergen J. P. The Drosophila segmentation gene runt encodes a novel nuclear regulatory protein that is also expressed in the developing nervous system. Genes Dev. 1990 Oct;4(10):1701–1713. doi: 10.1101/gad.4.10.1701. [DOI] [PubMed] [Google Scholar]
  20. Ko L. J., Yamamoto M., Leonard M. W., George K. M., Ting P., Engel J. D. Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. Mol Cell Biol. 1991 May;11(5):2778–2784. doi: 10.1128/mcb.11.5.2778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Le Beau M. M., Larson R. A., Bitter M. A., Vardiman J. W., Golomb H. M., Rowley J. D. Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association. N Engl J Med. 1983 Sep 15;309(11):630–636. doi: 10.1056/NEJM198309153091103. [DOI] [PubMed] [Google Scholar]
  22. Leiden J. M. Transcriptional regulation of T cell receptor genes. Annu Rev Immunol. 1993;11:539–570. doi: 10.1146/annurev.iy.11.040193.002543. [DOI] [PubMed] [Google Scholar]
  23. Liu P., Tarlé S. A., Hajra A., Claxton D. F., Marlton P., Freedman M., Siciliano M. J., Collins F. S. Fusion between transcription factor CBF beta/PEBP2 beta and a myosin heavy chain in acute myeloid leukemia. Science. 1993 Aug 20;261(5124):1041–1044. doi: 10.1126/science.8351518. [DOI] [PubMed] [Google Scholar]
  24. Marine J., Winoto A. The human enhancer-binding protein Gata3 binds to several T-cell receptor regulatory elements. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7284–7288. doi: 10.1073/pnas.88.16.7284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mitani K., Ogawa S., Tanaka T., Miyoshi H., Kurokawa M., Mano H., Yazaki Y., Ohki M., Hirai H. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J. 1994 Feb 1;13(3):504–510. doi: 10.1002/j.1460-2075.1994.tb06288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miyoshi H., Kozu T., Shimizu K., Enomoto K., Maseki N., Kaneko Y., Kamada N., Ohki M. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J. 1993 Jul;12(7):2715–2721. doi: 10.1002/j.1460-2075.1993.tb05933.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Miyoshi H., Shimizu K., Kozu T., Maseki N., Kaneko Y., Ohki M. t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10431–10434. doi: 10.1073/pnas.88.23.10431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Nucifora G., Begy C. R., Erickson P., Drabkin H. A., Rowley J. D. The 3;21 translocation in myelodysplasia results in a fusion transcript between the AML1 gene and the gene for EAP, a highly conserved protein associated with the Epstein-Barr virus small RNA EBER 1. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7784–7788. doi: 10.1073/pnas.90.16.7784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ogawa E., Inuzuka M., Maruyama M., Satake M., Naito-Fujimoto M., Ito Y., Shigesada K. Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology. 1993 May;194(1):314–331. doi: 10.1006/viro.1993.1262. [DOI] [PubMed] [Google Scholar]
  30. Ogawa E., Maruyama M., Kagoshima H., Inuzuka M., Lu J., Satake M., Shigesada K., Ito Y. PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6859–6863. doi: 10.1073/pnas.90.14.6859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Oosterwegel M., van de Wetering M., Dooijes D., Klomp L., Winoto A., Georgopoulos K., Meijlink F., Clevers H. Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers. J Exp Med. 1991 May 1;173(5):1133–1142. doi: 10.1084/jem.173.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sakakura C., Yamaguchi-Iwai Y., Satake M., Bae S. C., Takahashi A., Ogawa E., Hagiwara A., Takahashi T., Murakami A., Makino K. Growth inhibition and induction of differentiation of t(8;21) acute myeloid leukemia cells by the DNA-binding domain of PEBP2 and the AML1/MTG8(ETO)-specific antisense oligonucleotide. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11723–11727. doi: 10.1073/pnas.91.24.11723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Satake M., Inuzuka M., Shigesada K., Oikawa T., Ito Y. Differential expression of subspecies of polyomavirus and murine leukemia virus enhancer core binding protein, PEBP2, in various hematopoietic cells. Jpn J Cancer Res. 1992 Jul;83(7):714–722. doi: 10.1111/j.1349-7006.1992.tb01971.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Speck N. A., Renjifo B., Golemis E., Fredrickson T. N., Hartley J. W., Hopkins N. Mutation of the core or adjacent LVb elements of the Moloney murine leukemia virus enhancer alters disease specificity. Genes Dev. 1990 Feb;4(2):233–242. doi: 10.1101/gad.4.2.233. [DOI] [PubMed] [Google Scholar]
  35. Thornell A., Hallberg B., Grundström T. Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3. Mol Cell Biol. 1988 Apr;8(4):1625–1637. doi: 10.1128/mcb.8.4.1625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Travis A., Amsterdam A., Belanger C., Grosschedl R. LEF-1, a gene encoding a lymphoid-specific protein with an HMG domain, regulates T-cell receptor alpha enhancer function [corrected]. Genes Dev. 1991 May;5(5):880–894. doi: 10.1101/gad.5.5.880. [DOI] [PubMed] [Google Scholar]
  37. Wang S. W., Speck N. A. Purification of core-binding factor, a protein that binds the conserved core site in murine leukemia virus enhancers. Mol Cell Biol. 1992 Jan;12(1):89–102. doi: 10.1128/mcb.12.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wang S., Wang Q., Crute B. E., Melnikova I. N., Keller S. R., Speck N. A. Cloning and characterization of subunits of the T-cell receptor and murine leukemia virus enhancer core-binding factor. Mol Cell Biol. 1993 Jun;13(6):3324–3339. doi: 10.1128/mcb.13.6.3324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Waterman M. L., Fischer W. H., Jones K. A. A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer. Genes Dev. 1991 Apr;5(4):656–669. doi: 10.1101/gad.5.4.656. [DOI] [PubMed] [Google Scholar]
  40. Waterman M. L., Jones K. A. Purification of TCF-1 alpha, a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner. New Biol. 1990 Jul;2(7):621–636. [PubMed] [Google Scholar]
  41. Wotton D., Ghysdael J., Wang S., Speck N. A., Owen M. J. Cooperative binding of Ets-1 and core binding factor to DNA. Mol Cell Biol. 1994 Jan;14(1):840–850. doi: 10.1128/mcb.14.1.840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]
  43. van de Wetering M., Oosterwegel M., Dooijes D., Clevers H. Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box. EMBO J. 1991 Jan;10(1):123–132. doi: 10.1002/j.1460-2075.1991.tb07928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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