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Isolation and characterization of the human A-myb promoter: regulation by NF-Y and Sp1

Oncogene volume 19, pages 3931–3940 (2000)Cite this article

Abstract

The A-myb transcription factor shows a restricted tissue distribution and is cell cycle regulated. Furthermore its deregulation has profound effects on the growth and/or differentiation of the cells in which it is normally expressed. We have therefore characterized its promoter. A 12 kb genomic clone was isolated that comprises the first exon, part of the first intron as well as upstream regulatory sequences. Multiple transcription start sites have been identified which operate in both B lymphocytes and epithelial cells and the upsteam region was shown to have promoter, activity. The boundaries of the minimal promoter region (−183−14), of a positive upstream (−538−183) and a negative downstream regulatory region (NRE) (+83+374) have been defined. The NRE is promoter- and orientation-independent but position specific. The A-myb minimal promoter is GC-rich, does not contain any TATA box but has a functional CCAAT box. The CCAAT box and minimal promoter is highly conserved in the corresponding murine sequence. The CCAAT box efficiently binds the NF-Y complex and its mutation decreases basal promoter activity by 50%. Two Sp1 binding sites are present upstream from the CCAAT box which can bind Sp1 and contribute to A-myb promoter activity by 70 and 30%, respectively. The two Sp1 sites and CCAAT box together contribute to over 80% of A-myb basal promoter activity and are therefore the major regulatory elements. Finally, we show that the promoter is cell cycle regulated and that the SP1 and CCAAT elements are required for S phase induction.

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References

  • Birnbaum MJ, van Wijnen AJ, Odgren PR, Last TJ, Suske G, Stein GS and Stein JL. . 1995 Biochem. 34: 16503–16508.

  • Black AR, Jensen D, Lin S-Y and Azizkhan JC. . 1999 J. Biol. Chem. 274: 1207–1215.

  • Blackwood EM and Kadonaga KT. . 1998 Science 281: 60–63.

  • Bolognese F, Wasner M, Lange-zu Dohna C, Gurtner A, Ronchi A, Muller H, Manni I, Mossner J, Piaggio G, Mantovani R and Engeland K. . 1999 Oncogene 18: 1845–1853.

  • Busslinger M, Klix N, Pfeffer P, Granninger PG and Kozmik Z. . 1996 Proc. Natl. Acad. Sci. USA. 93: 6129–6134.

  • Datta AK. . 1995 Nucleic. Acids. Res. 23: 4530–4531.

  • DeRocco SE, Iozzo R, Ma XP, Schwarting R, Peterson D and Calabretta B. . 1997 Proc. Natl. Acad. Sci. USA. 94: 3240–3244.

  • Dorn A, Bollekens J, Staub A, Benoist C and Mathis D. . 1987 Cell 50: 863–872.

  • Farina A, Manni I, Fontemaggi G, Tiainen M, Cenciarelli C, Bellorini M, Mantovani R, Sacchi A and Piaggio G. . 1999 Oncogene 18: 2818–2827.

  • Foos G, Grimm S and Klempnauer KH. . 1994 Oncogene 9: 2481–2488.

  • Golay J, Broccoli V, Lamorte G, Bifulco C, Parravicini C, Thomas NSB, Delia D, Ferrauti P, Vitolo D and Introna M. . 1998 J. Immunol. 160: 2786–2793.

  • Golay J, Erba E, Bernasconi S, Peri G and Introna M. . 1994a J. Immunol. 153: 543–553.

  • Golay J, Facchinetti V, Ying G-G and Introna M. . 1997 Leuk. Lymphoma 26: 271–279.

  • Golay J, Loffarelli L, Luppi M, Castellano M and Introna M. . 1994b Oncogene 9: 2469–2479.

  • Golay J, Luppi M, Songia S, Palvarini C, Lombardi L, Aiello A, Delia D, Lam K, Crawford DH, Biondi A, Barbui T, Rambaldi A and Introna M. . 1996 Blood 87: 1900–1911.

  • Gonda TJ, Cory S, Sobieszczuk P, Holtzman D and Adams JM. . 1987 J. Virol. 61: 2754–2763.

  • Graf T. . 1992 Curr. Opin. Genet. Dev. 2: 249–255.

  • Huet X, Rech J, Plet A, Vié A and Blanchard JM. . 1996 Mol. Cell Biol. 16: 3789–3798.

  • Introna M, Luchetti M, Castellano M, Arsura M and Golay J. . 1994 Sem. Cancer. Biol. 5: 113–124.

  • Karlseder J, Rotheneder H and Wintersberger E. . 1996 Mol. Cell Biol. 16: 1659–1667.

  • Latham KE, Litvin J, Orth JM, Patel B, Mettus R and Reddy EP. . 1996 Oncogene 13: 1161–1168.

  • Lin S-Y, Black AR, Kostic D, Pajovic S, Hoover CN and Azizkhan JC. . 1996 Mol. Cell. Biol. 16: 1668–1675.

  • Maity SN and de Combrugghe B. . 1998 Trends Biochem. 23: 174–178.

  • Mantovani R. . 1998 Nucleic. Acids. Res. 26: 1135–1143.

  • Mantovani R, Pessara U, Tronche F, Li XY, Knapp AM, Pasquali JL, Benoist C and Mathis D. . 1992 EMBO J. 11: 3315–3322.

  • Marhamati DJ, Bellas RE, Arsura M, Kypreos KE and Sonenshein GE. . 1997 Mol. Biol. Cell 17: 2448–2457.

  • Mettus RV, Litvin J, Wali A, Toscani A, Latham K, Hatton K and Reddy EP. . 1994 Oncogene 9: 3077–3086.

  • Noe V, Alemany C, Chasin LA and Ciudad CJ. . 1998 Oncogene 16: 1931–1938.

  • Nomura N, Takahashi M, Matsui M, Ishii S, Date T, Sasamoto S and Ishizaki R. . 1988 Nucleic. Acids. Res. 16: 11075–11089.

  • Noti JD, Reinemann BC and Petrus MN. . 1996 Mol. Cell Biol. 16: 2940–2950.

  • Oh I-H and Reddy EP. . 1997 J. Biol. Chem. 272: 21432–21443.

  • Oh I-H and Reddy EP. . 1999 Oncogene 18: 3017–3033.

  • Pugh BF and Tjian R. . 1991 Genes & Dev. 5: 1935–1945.

  • Rabbits TH. . 1994 Nature 372: 143–149.

  • Roder K, Wolf SS, Beck K-F and Schweizer M. . 1997 J. Biol. Chem. 272: 21616–21624.

  • Sala A, Saitta B, De Luca P, Cervellera MN, Casella I, Lewis RE, Watson R and Peschle C. . 1999 Oncogene 18: 1333–1339.

  • Saville MK and Watson RJ. . 1998 Adv. Cancer Res. 72: 109–140.

  • Seto M, Jaeger U, Hockett RD, Graninger W, Bennett S, Goldman P and Korsmeter SJ. . 1988 EMBO J. 7: 123–131.

  • Smith CL and Hager GL. . 1997 J. Biol. Chem. 272: 27493–27496.

  • Sundseth R, MacDonald G, Ting J and King AC. . 1997 Mol. Pharmacol. 51: 963–971.

  • Takahashi T, Nakagoshi H, Sarai A, Nomura N, Yamamoto T and Ishii S. . 1995 FEBS. Lett. 358: 89–96.

  • Toscani A, Mettus RV, Coupland R, Simpkins H, Litvin J, Orth J, Hatton KS and Reddy EP. . 1997 Nature 386: 713–717.

  • Trauth K, Mutschler B, Jenkins NA, Gilbert DJ, Copeland NG and Klempnauer KH. . 1994 EMBO J. 13: 5994–6005.

  • Udvadia AJ, Rogers KT, Higgins PD, Murata Y, Martin KH, Humphrey PA and Horowitz JM. . 1993 Proc. Natl. Acad. Sci. 90: 3265–3269.

  • van Ginkel PR, Hsiao KM, Schjerven H and Farnham PJ. . 1999 J. Biol. Chem. 272: 18367–18374.

  • Wells J, Held P, Illenye S and Heintz NH. . 1996 Mol. Cell. Biol. 16: 634–647.

  • Wright KL, Moore TL, Vilen BJ, Brown AM and Ting JPY. . 1995 J. Biol. Chem. 270: 20978–20986.

  • Ying G-G, Arsura M, Introna M and Golay J. . 1997 J. Biol. Chem. 272: 24921–24926.

  • Young RL and Korsmeyer SJ. . 1993 Mol. Cell Biol. 13: 3686–3697.

  • Ziebold U and Klempnauer K-H. . 1997 Oncogene 15: 1011–1019.

  • Zwicker J, Gross C, Lucibello FC, Truss M, Ehlert F, Engeland K and Müller R. . 1995a Nucleic. Acids. Res. 23: 3822–3830.

  • Zwicker J, Lucibello FC, Wolfraim LA, Gross C, Truss M, Engeland K and Müller R. . 1995b EMBO J. 14: 4514–4522.

  • Zwicker J and Müller R. . 1997 Trends Genet. 13: 3–6.

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Acknowledgements

This work was supported in part by the Italian Association for Cancer Research to M Introna and R Mantovani (A.I.R.C.), and by the ‘Istituto Superiore di Sanità’ (I.S.S., Rome, Italy; AIDS grant no. 30B.29). V Facchinetti is a Fellow F.B. 1998-2000.

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Authors and Affiliations

  1. Department of Immunology and Cell Biology, Laboratory of Molecular Immunohaematology, Istituto Ricerche Farmacologiche Mario Negri, via Eritrea 62, 20157 Milan, Italy

    V Facchinetti, R Lopa, F Spreafico, M Introna & J Golay

  2. Department of Genetics and Biology of Microorganisms, University of Milan, via Celoria 26, 20133 Milan, Italy

    F Bolognese & R Mantovani

  3. Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, Norfolk Place, London, W2 1PG, UK

    F Tavner & R Watson

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  1. V Facchinetti
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Facchinetti, V., Lopa, R., Spreafico, F. et al. Isolation and characterization of the human A-myb promoter: regulation by NF-Y and Sp1. Oncogene 19, 3931–3940 (2000). https://doi.org/10.1038/sj.onc.1203730

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