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The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase

Oncogene volume 20, pages 404–409 (2001)Cite this article

Abstract

The monocytic leukemia zinc finger protein (MOZ) gene is rearranged in t(8;16)(p11;p13), t(8;22)(p11;q13) and inv(8)(p11q13) associated with acute myeloid leukemia. The other fusion partners involved are CBP, p300 and TIF2, transcriptional coactivators with known or potential histone acetyltransferase (HAT) activity. MOZ itself is a 2004-residue protein containing a putative acetyl CoA-binding motif, so it was hypothesized that MOZ is a HAT. Here we present direct evidence that MOZ has intrinsic HAT activity. Moreover, MOZ possesses a transcriptional repression domain at its N-terminal part and an activation domain at its C-terminal part. The activation domain does not show sequence similarity to any yeast proteins, but when tethered, it is able to activate transcription in yeast. Therefore, MOZ is a HAT with characteristics of a transcriptional coregulator, supporting the hypothesis that aberrant acetylation by abnormal MOZ proteins leads to leukemogenesis.

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References

  • Akhtar A and Becker PB. . 2000 Mol. Cell 5: 367–375.

  • Allard S, Utley RT, Savard J, Clarke A, Grant P, Brandl CJ, Pillus L, Workman JL and Cote J. . 1999 EMBO J. 18: 5108–5119.

  • Bannister AJ and Kouzarides T. . 1996 Nature 384: 641–643.

  • Borrow J, Stanton Jr. VP, Andresen JM, Becher R, Behm FG, Chaganti RS, Civin CI, Disteche C, Dube I, Frischauf AM, Horsman D, Mitelman F, Volinia S, Watmore AE and Housman DE. . 1996 Nat. Genet. 14: 33–41.

  • Brownell JE, Zhou J, Ranalli T, Kobayashi R, Edmondson DG, Roth SY and Allis CD. . 1996 Cell 84: 843–851.

  • Carapeti M, Aguiar RC, Goldman JM and Cross NC. . 1998 Blood 91: 3127–3133.

  • Carapeti M, Aguiar RC, Watmore AE, Goldman JM and Cross NC. . 1999 Cancer Genet. Cytogenet. 113: 70–72.

  • Chaffanet M, Gressin L, Preudhomme C, Soenen-Cornu V, Birnbaum D and Pebusque MJ. . 2000 Genes Chrom. Cancer 28: 138–144.

  • Chaffanet M, Mozziconacci MJ, Fernandez F, Sainty D, Lafage-Pochitaloff M, Birnbaum D and Pebusque MJ. . 1999 Genes Chromosomes Cancer 26: 161–165.

  • Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y, Heng HH and Yang XJ. . 1999 J. Biol. Chem. 274: 28528–28536.

  • Chen H, Lin RJ, Schiltz RL, Chakravati D, Nash A, Nagy L, Privalsky ML, Nakatani Y and Evans RM. . 1997 Cell 90: 569–580.

  • Clarke AS, Lowell JE, Jacobson SJ and Pillus L. . 1999 Mol. Cell. Biol. 19: 2515–2526.

  • Galarneau L, Nourani A, Boudreault AA, Zhang Y, Heliot L, Allard S, Savard J, Lane WS, Stillman D and Cote J. . 2000 Mol. Cell 5: 927–937.

  • Hilfiker A, Hilfiker-Kleiner D, Pannuti A and Lucchesi JC. . 1997 EMBO J. 16: 2054–2060.

  • Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M and Hayashi Y. . 1997 Blood 90: 4699–4704.

  • Iizuka M and Stillman B. . 1999 J. Biol. Chem. 274: 23027–23034.

  • Ikura T, Ogryzko VV, Grigoriev M, Groisman R, Wang J, Horikoshi M, Scully R, Qin J and Nakatani Y. . 2000 Cell 102: 463–473.

  • Jacobson S and Pillus L. . 1999 Curr. Opin. Gent. Dev. 9: 175–184.

  • John S, Howe L, Tafrov ST, Grant PA, Sternglanz R and Workman JL. . 2000 Genes Dev. 14: 1196–1208.

  • Kornberg RD and Lorch Y. . 1999 Cell 98: 285–294.

  • Kuo M-H and Allis CD. . 1998 Bio. Essays 20: 615–626.

  • Liang J, Prouty L, Williams BJ, Dayton MA and Blanchard KL. . 1998 Blood 92: 2118–2122.

  • Mizzen CA, Yang XJ, Kokubo T, Brownell JE, Bannister AJ, Owen-Hughes T, Workman J, Wang L, Berger SL, Kouzarides T, Nakatani Y and Allis CD. . 1996 Cell 87: 1261–1270.

  • Neal KC, Pannuti A, Smith ER and Lucchesi JC. . 2000 Biochim. Biophys. Acta. 1490: 170–174.

  • Ogryzko VV, Schiltz RL, Russanova V, Howard BH and Nakatani Y. . 1996 Cell 87: 953–959.

  • Reifsnyder C, Lowell J, Clarke A and Pillus L. . 1996 Nat. Genet. 14: 42–49.

  • Rowley JD, Reshmi S, Sobulo O, Musvee T, Anastasi J, Raimondi S, Schneider NR, Barredo JC, Cantu ES, Schlegelberger B, Behm F, Doggett NA, Borrow J and Zeleznik-Le N. . 1997 Blood 90: 535–541.

  • Satake N, Ishida Y, Hinohara S, Kobayashi H, Sakashita A, Maseki N and Kaneko Y. . 1997 Genes Chrom. Cancer 20: 60–63.

  • Sharma M, Zarnegar M, Li X, Lim B and Sun J. . 2000 J. Biol. Chem. 275: 35200–35208.

  • Smith ER, Eisen A, Gu W, Sattah M, Pannuti A, Zhou J, Cook RG, Lucchesi JC and Allis CD. . 1998 Proc. Natl. Acad. Sci. USA 95: 3561–3565.

  • Smith ER, Pannuti A, Gu W, Steurnagel A, Cook RG, Allis CD and Lucchesi JC. . 1999 Mol. Cell. Biol. 20: 312–318.

  • Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegeberger B, Housman D, Doggett NA, Rowley JD and Zeleznikle NJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 8732–8737.

  • Spencer TE, Jenster G, Burcin MM, Allis CD, Zhou J, Mizzen CA, Mckenna NJ, Onate SA, Tsai SY, Tsai M-J and O'Malley BW. . 1997 Nature 389: 194–197.

  • Sterner DE and Berger SL. . 2000 Microbiol. Mol. Biol. Rev. 64: 435–459.

  • Struhl K. . 1998 Genes Dev. 12: 599–606.

  • Swope DL, Mueller CL and Chrivia JC. . 1996 J. Biol. Chem. 271: 28138–28145.

  • Takechi S and Nakayama T. . 1999 Biochem. Biophys. Res. Commun. 266: 405–410.

  • Taki T, Sako M, Tsuchida M and Hayashi Y. . 1997 Blood 89: 3945–3950.

  • Thomas T, Voss AK, Chowdhury K and Gruss P. . 2000 Development 127: 2537–2548.

  • Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J and Yang XJ. . 1999 Mol. Cell. Biol. 19: 7816–7827.

  • Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP and Yang XJ. . 2000 Mol. Cell. Biol. 20: 6904–6912.

  • West RW, Yocum RR and Ptashne M. . 1984 Mol. Cell. Biol. 4: 2467–2478.

  • Wolffe AP, Wong J and Pruss D. . 1997 Genes Cells 2: 291–302.

  • Workman JL and Kingston RE. . 1998 Annu. Rev. Biochem. 67: 545–579.

  • Yamamoto T and Horikoshi M. . 1997 J. Biol. Chem. 272: 30595–30598.

  • Yang XJ, Ogryzko VV, Nishikawa J, Howard BH and Nakatani Y. . 1996 Nature 382: 319–324.

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Acknowledgements

We thank M Ptashne and E Moore for the reporter plasmid pLR1Δ 1 and J Côté for HeLa histones. This work was supported by a fellowship from Fonds de la recherche en santé du Québec (FRSQ) (to N Champagne), grants from the National Cancer Institute of Canada and a scholarship from the Medical Research Council of Canada (to X-J Yang).

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  1. Department of Medicine, Molecular Oncology Group, McGill University Health Centre, Montréal, Québec, H3A 1A1, Canada

    Nathalie Champagne, Nadine Pelletier & Xiang-Jiao Yang

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Champagne, N., Pelletier, N. & Yang, XJ. The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene 20, 404–409 (2001). https://doi.org/10.1038/sj.onc.1204114

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