MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2
MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2
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DOI：
10.1038/sj.onc.1205367
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发表时间：
2002-04-18
期刊：
影响因子：
8
通讯作者：
Yang, XJ
中科院分区：
文献类型：
--
作者：
Pelletier, N;Champagne, N;Yang, XJ
单核细胞白血病锌指蛋白MOZ及其同源物Morf与白血病的发生有关。MoZ和Morf都是组蛋白乙酰转移酶，具有较弱的转录抑制结构域和较强的转录激活结构域，提示它们可能作为转录共调节因子发挥作用。在这里，我们描述了Moz和Morf都与Runx2(或Cbfa1)相互作用，Runx2(或Cbfa1)是一种已知在T细胞淋巴肿大和骨发育中发挥重要作用的Run结构域转录因子。通过其C-末端SM(富含丝氨酸和蛋氨酸)结构域，Morf在体外和体内与Runx2结合。与此一致的是，Morf的SM结构域也与RUNX1(或AML1)结合，Runx2同源物经常因白血病相关的染色体易位而改变。虽然Morf不乙酰化Runx2，但其SM结构域增强了Runx2依赖的转录激活。此外，内源性Morf是Runx2转录激活所必需的。有趣的是，Runx2负向调节SM结构域的转录激活潜力。与Morf类似，Moz的SM结构域在物理上和功能上都与Runx2相互作用。因此，这些结果表明Runx2是MoZ和Morf的相互作用伙伴，并表明这两种乙酰基转移酶都参与了Runx2及其同系物介导的转录激活的调节。
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.