MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2.
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.
Pelletier
Nadine
N
Molecular Oncology Group, Department of Medicine, McGill University Health Center, Quebec, Canada.
Champagne
Nathalie
N
Stifani
Stefano
S
Yang
Xiang-Jiao
XJ
D016475:3T3 Cells; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016367:Baculoviridae / Q000502:physiology; D050659:Core Binding Factor Alpha 1 Subunit; D051548:Histone Acetyltransferases; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010455:Peptides; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010455:Peptides; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C085706:FLAG peptide; D008156:Luciferases; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human