Abstract
The monocytic leukemia zinc finger protein MOZ and its homologue MORF have been implicated in leukemogenesis. Both MOZ and MORF are histone acetyltransferases with weak transcriptional repression domains and strong transcriptional activation domains, suggesting that they may function as transcriptional coregulators. Here we describe that MOZ and MORF both interact with Runx2 (or Cbfa1), a Runt-domain transcription factor that is known to play important roles in T cell lymphomagenesis and bone development. Through its C-terminal SM (serine- and methionine-rich) domain, MORF binds to Runx2 in vitro and in vivo. Consistent with this, the SM domain of MORF also binds to Runx1 (or AML1), a Runx2 homologue that is frequently altered by leukemia-associated chromosomal translocations. While MORF does not acetylate Runx2, its SM domain potentiates Runx2-dependent transcriptional activation. Moreover, endogenous MORF is required for transcriptional activation by Runx2. Intriguingly, Runx2 negatively regulates the transcriptional activation potential of the SM domain. Like that of MORF, the SM domain of MOZ physically and functionally interacts with Runx2. These results thus identify Runx2 as an interaction partner of MOZ and MORF and suggest that both acetyltransferases are involved in regulating transcriptional activation mediated by Runx2 and its homologues.
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References
Akhtar A, Becker PB . 2000 Mol. Cell 5: 367–375
Akhtar A, Zink D, Becker PB . 2000 Nature 407: 405–409
Allard S, Utley RT, Savard J, Clarke A, Grant P, Brandl CJ, Pillus L, Workman JL, Cote J . 1999 EMBO J. 18: 5108–5119
Aronson BD, Fisher AL, Blechman K, Caudy M, Gergen JP . 1997 Mol. Cell. Biol. 17: 5581–5587
Blyth K, Terry A, Mackay N, Vaillant F, Bell M, Cameron ER, Neil JC, Stewart M . 2001 Oncogene 20: 295–302
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, Housman De . 1996 Nat. Genet. 14: 33–41
Brady ME, Ozanne DM, Gaughan L, Waite I, Cook S, Neal DE, Robson CN . 1999 J. Biol. Chem. 274: 17599–17604
Brown CE, Howe L, Sousa K, Alley SC, Carrozza MJ, Tan S, Workman JL . 2001 Science 292: 2333–2337
Brown CE, Lechner T, Howe L, Workman JL . 2000 Trends Biochem. Sci. 25: 15–19
Burke TW, Cook JG, Asano M, Nevins JR . 2001 J. Biol. Chem. 276: 15397–15408
Cao X, Sudhof TC . 2001 Science 293: 115–120
Carapeti M, Aguiar RC, Goldman JM, Cross NC . 1998 Blood 91: 3127–3133
Carapeti M, Aguiar RC, Watmore AE, Goldman JM, Cross NC . 1999 Cancer Genet. Cytogenet. 113: 70–72
Chaffanet M, Gressin L, Preudhomme C, Soenen-Cornu V, Birnbaum D, Pebusque MJ . 2000 Genes Chrom. Cancer 28: 138–144
Chaffanet M, Mozziconacci MJ, Fernandez F, Sainty D, Lafage-Pochitaloff M, Birnbaum D, Pebusque MJ . 1999 Genes Chrom. Cancer 26: 161–165
Champagne N, Bertos NR, Pelletier N, Wang AH, Vezmar M, Yang Y, Heng HH, Yang XJ . 1999 J. Biol. Chem. 274: 28528–28536
Champagne N, Pelletier N, Yang XJ . 2001 Oncogene 20: 404–409
Clarke AS, Lowell JE, Jacobson SJ, Pillus L . 1999 Mol. Cell. Biol. 19: 2515–2526
Ducy P, Karsenty G . 1995 Mol. Cell. Biol. 15: 1858–1869
Ducy P, Schinke T, Karsenty G . 2000 Science 289: 1501–1504
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T . 2001 Nature 411: 494–498
Galarneau L, Nourani A, Boudreault AA, Zhang Y, Heliot L, Allard S, Savard J, Lane WS, Stillman DJ, Cote J . 2000 Mol. Cell 5: 927–937
Hassan AH, Neely KE, Workman JL . 2001 Cell 104: 817–827
Hilfiker A, Hilfiker-Kleiner D, Pannuti A, Lucchesi JC . 1997 EMBO J. 16: 2054–2060
Howe L, Auston D, Grant P, John S, Cook RG, Workman JL, Pillus L . 2001 Genes Dev. 15: 3144–3154
Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y . 1997 Blood 90: 4699–4704
Iizuka M, 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, Nakatani Y . 2000 Cell 102: 463–473
Jacobson S, Pillus L . 1999 Curr. Opin. Genet. Dev. 9: 175–184
Jenuwein T, Allis CD . 2001 Science 293: 1074–1080
John S, Howe L, Tafrov ST, Grant PA, Sternglanz R, Workman JL . 2000 Genes Dev. 14: 1196–1208
Kamine J, Elangovan B, Subramanian T, Coleman D, Chinnadurai G . 1996 Virology 216: 357–366
Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, Hisaminato A, Fujiwara T, Ito Y, Cantley LC, Yaffe MB . 2000 EMBO J. 19: 6778–6791
Kitabayashi I, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M . 2001a EMBO J. 20: 7184–7196
Kitabayashi I, Aikawa Y, Yokoyama A, Hosoda F, Nagai M, Kakazu N, Abe T, Ohki M . 2001b Leukemia 15: 89–94
Kitabayashi I, Yokoyama A, Shimizu K, Ohki M . 1998 EMBO J. 17: 2994–3004
Kouzarides T . 2000 EMBO J. 19: 1176–1179
Lavau C, Du C, Thirman M, Zeleznik-Le N . 2000 EMBO J. 19: 4655–4664
Lee HJ, Chun M, Kandror KV . 2001 J. Biol. Chem. 276: 16597–16600
Liang J, Prouty L, Williams BJ, Dayton MA, Blanchard KL . 1998 Blood 92: 2118–2122
Look AT . 1997 Science 278: 1059–1064
Lutterbach B, Westendorf JJ, Linggi B, Isaac S, Seto E, Hiebert SW . 2000 J. Biol. Chem. 275: 651–656
McLarren KW, Lo R, Grbavec D, Thirunavukkarasu K, Karsenty G, Stifani S . 2000 J. Biol. Chem. 275: 530–538
McLarren KW, Theriault FM, Stifani S . 2001 J. Biol. Chem. 276: 1578–1584
Meijsing SH, Ehrenhofer-Murray AE . 2001 Genes Dev. 15: 3169–3182
Mizzen CA, Yang XJ, Kokubo T, Brownell JE, Bannister AJ, Owen-Hughes T, Workman J, Wang L, Berger SL, Kouzarides T, Nakatani Y, Allis CD . 1996 Cell 87: 1261–1270
Nakatina Y . 2001 Genes Cell 6: 79–86
Osada S, Sutton A, Muster N, Brown CE, Yates III JR, Sternglanz R, Workman JL . 2001 Genes Dev. 15: 3155–3168
Panagopoulos I, Fioretos T, Isaksson M, Samuelsson U, Billstrom R, Strombeck B, Mitelman F, Johansson B . 2001 Hum. Mol. Genet. 10: 395–404
Panagopoulos I, Isaksson M, Lindvall C, Bjorkholm M, Ahlgren T, Fioretos T, Heim S, Mitelman F, Johansson B . 2000 Genes Chrom. Cancer 28: 415–424
Ran Q, Pereira-Smith OM . 2000 Gene 258: 141–146
Reid JL, Iyer VR, Brown PO, Struhl K . 2000 Mol. Cell 6: 1297–1307
Reifsnyder C, Lowell J, Clarke A, 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, Zeleznik-Le N . 1997 Blood 90: 535–541
Satake N, Ishida Y, Otoh Y, Hinohara S, Kobayashi H, Sakashita A, Maseki N, Kaneko Y . 1997 Genes Chrom. Cancer 20: 60–63
Scott EK, Lee T, Luo L . 2001 Curr. Biol. 11: 99–104
Semenza GL . 1998 Transcription factors and human diseases. Medical Genetics. No. 37 Motulsky AG, Bobrow M, Harper PS and Scriver C (eds) New York, Oxford: Oxford University Press
Sharma M, Zarnegar M, Li X, Lim B, Sun Z . 2000 J. Biol. Chem. 275: 35200–35208
Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV . 2001 Mol. Cell. Biol. 21: 4470–4481
Smith ER, Eisen A, Gu W, Sattah M, Pannutti A, Zhou J, Cook RG, Lucchesi JC, Allis CD . 1998 Proc. Natl. Acad. Sci. USA 95: 3561–3565
Sobulo OM, Borrow J, Tomek R, Reshmi S, Harden A, Schlegelberger B, Housman D, Doggett NA, Rowley JD, Zeleznik-Le NJ . 1997 Proc. Natl. Acad. Sci. USA 94: 8732–8737
Speck NA, Stacy T, Wang Q, North T, Gu TL, Miller J, Binder M, Marin-Padilla M . 1999 Cancer Res. 59: 1789–1793
Sterner DE, Berger SL . 2000 Microbiol. Mol. Biol. Rev. 64: 435–459
Strom DK, Nip J, Westerndorf JJ, Linggi B, Lutterbach B, Downing JR, Lenny N, Hiebert SW . 2000 J. Biol. Chem. 275: 3438–3445
Takechi S, Nakayama T . 1999 Biochem. Biophys. Res. Commun. 266: 405–410
Taki T, Sako M, Tsuchida M, Hayashi Y . 1997 Blood 89: 3945–3950
Thirunavukkarasu K, Mahajan M, McLarren KW, Stifani S, Karsenty G . 1998 Mol. Cell. Biol. 18: 4197–4208
Thomas T, Voss AK, Chowdhury K, Gruss P . 2000 Development 127: 2537–2548
Vaillant F, Blyth K, Terry A, Bell M, Cameron ER, Neil J, Stewart M . 1999 Oncogene 18: 7124–7134
Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ . 1999 Mol. Cell. Biol. 19: 7816–7827
Wang AH, Kruhlak MJ, Wu J, Bertos NR, Vezmar M, Posner BI, Bazett-Jones DP, Yang XJ . 2000 Mol. Cell. Biol. 20: 6904–6912
Westendorf JJ, Hiebert SW . 1999 J. Cell. Biochem. 32: 51–58
Wheeler JC, Shigesada K, Gergen JP, Ito Y . 2000 Semin. Cell Dev. Biol. 11: 369–375
Yagi R, Chen LF, Shigesada K, Murakami Y, Ito Y . 1999 EMBO J. 18: 2551–2562
Yamamoto T, Horikoshi M . 1997 J. Biol. Chem. 272: 30595–30598
Yan Y, Barlev NA, Haley RH, Berger SL, Marmorstein R . 2000 Mol. Cell 6: 1195–1205
Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y . 1996 Nature 382: 319–324
Acknowledgements
We thank Dr G Karsenty for the wild-type Runx2 expression plasmid and the 6OSE2-Luc and OG2-Luc reporters. This work was supported by grants from the National Cancer Institute of Canada (X-J Yang), Canada Foundation for Innovation (X-J Yang) and the Canadian Institutes of Health Research (CIHR) (S Stifani). N Champagne and S Stifani are a postdoctoral fellow and a scholar of Fonds de la Recherche en Santé du Québec, respectively. X-J Yang is the recipient of a scholarship from the CIHR.
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Pelletier, N., Champagne, N., Stifani, S. et al. MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene 21, 2729–2740 (2002). https://doi.org/10.1038/sj.onc.1205367
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DOI: https://doi.org/10.1038/sj.onc.1205367
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