Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein

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Abstract
The AML1–CBFβ transcription factor complex is the most frequent target of specific chromosome translocations in human leukemia. The MOZ gene, which encodes a histone acetyltransferase (HAT), is also involved in some leukemia‐associated translocations. We report here that MOZ is part of the AML1 complex and strongly stimulates AML1‐mediated transcription. The stimulation of AML1‐mediated transcription is independent of the inherent HAT activity of MOZ. Rather, a potent transactivation domain within MOZ appears to be essential for stimulation of AML1‐mediated transcription. MOZ, as well as CBP and MOZ–CBP, can acetylate AML1 in vitro . The amount of AML1–MOZ complex increases during the differentiation of M1 myeloid cells into monocytes/macrophages, suggesting that the AML1–MOZ complex might play a role in cell differentiation. On the other hand, the MOZ–CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1‐mediated transcription and differentiation of M1 cells. These results suggest that MOZ–CBP might induce leukemia by antagonizing the function of the AML1 complex.