The monocytic leukemia zinc-finger protein (MOZ) gene is rearranged in t(8; 16)(p11; p13) and inv(8)(p11q13) associated with acute myeloid leukemia. The other fusion partners involved are CBP and TIF2, both of which are known transcriptional coactivators with intrinsic histone acetyltransferase activity. We have cloned MORF, a new human protein related to MOZ, and demonstrated that MOZ and MORF have intrinsic histone acetyltransferase activity. Moreover, like MORF, MOZ possesses a weak transcriptional repression domain at its N-terminal part and a strong activation domain at its C-terminal part. These results indicate that MOZ and MORF are acetyltransferases involved in regulating transcription and thereby shed light on how aberrant MOZ proteins lead to leukemogenesis.