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  • Original Paper
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MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2

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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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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Correspondence to Xiang-Jiao Yang.

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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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