The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase.

The monocytic leukemia zinc finger protein (MOZ) gene is rearranged in t(8;16)(p11;p13), t(8;22)(p11;q13) and inv(8)(p11q13) associated with acute myeloid leukemia. The other fusion partners involved are CBP, p300 and TIF2, transcriptional coactivators with known or potential histone acetyltransferase (HAT) activity. MOZ itself is a 2004-residue protein containing a putative acetyl CoA-binding motif, so it was hypothesized that MOZ is a HAT. Here we present direct evidence that MOZ has intrinsic HAT activity. Moreover, MOZ possesses a transcriptional repression domain at its N-terminal part and an activation domain at its C-terminal part. The activation domain does not show sequence similarity to any yeast proteins, but when tethered, it is able to activate transcription in yeast. Therefore, MOZ is a HAT with characteristics of a transcriptional coregulator, supporting the hypothesis that aberrant acetylation by abnormal MOZ proteins leads to leukemogenesis.