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MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2
Nadine Pelletier1, Nathalie Champagne, Stefano Stifani
1Molecular Oncology Group, Department of Medicine, McGill University Health Center, Quebec, Canada.
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.
Insights
The monocytic leukemia zinc finger protein (MOZ) and its homologue (MORF) interact with Runx2, a transcription factor involved in T cell lymphoma and bone development. This interaction is crucial for regulating gene transcription in leukemogenesis.
Area of Science:
- Molecular Biology
- Cancer Biology
- Epigenetics
Background:
- The monocytic leukemia zinc finger protein (MOZ) and its homologue MORF are implicated in leukemogenesis.
- MOZ and MORF function as histone acetyltransferases with roles in transcriptional regulation.
- Runx2 is a transcription factor critical for T cell lymphomagenesis and bone development.
Purpose of the Study:
- To investigate the interaction between MOZ/MORF and Runx2.
- To elucidate the functional consequences of this interaction on transcriptional regulation.
- To determine the role of MOZ and MORF in Runx2-mediated gene expression.
Main Methods:
- In vitro and in vivo binding assays to assess protein-protein interactions.
- Analysis of transcriptional activation assays to evaluate functional consequences.
- Endogenous protein analysis to confirm physiological relevance.
Main Results:
- MOZ and MORF directly interact with Runx2 through their SM domains.
- The SM domain of MORF potentiates Runx2-dependent transcriptional activation.
- Endogenous MORF is required for Runx2-mediated transcription, and Runx2 negatively regulates the SM domain's activation potential.
- MOZ also physically and functionally interacts with Runx2.
Conclusions:
- Runx2 is identified as a novel interaction partner for MOZ and MORF.
- MOZ and MORF are involved in regulating transcriptional activation mediated by Runx2 and its homologues.
- These findings provide insights into the molecular mechanisms underlying leukemogenesis and bone development.