Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8;22)(p11;q13) chromosome translocation

Abstract

Histone acetyltransferase p300 functions as a transcriptional co-activator which interacts with a number of transcription factors. Monocytic leukemia zinc finger protein (MOZ) has histone acetyltransferase activity. We report the fusion of the MOZ gene to the p300 gene in acute myeloid leukemia with translocation t(8;22)(p11;q13). FISH and Southern blot analyses showed the rearrangement of the MOZ and p300 genes. We determined the genomic structure of the p300 and the MOZ genes and the breakpoints of the translocation. Analysis of fusion transcripts indicated that the zinc finger and acetyltransferase domains of MOZ are fused to a largely intact p300. These results suggest that MOZ-p300, which has two acetyltransferase domains, could be involved in leukemogenesis through aberrant regulation of histone acetylation. Leukemia (2001) 15, 89-94.

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

“…MOZ-CBP lacks the SM domain of MOZ, but gains almost all of CBP (Figure 3a). Mirroring the homology between p300 and CBP, the MOZ gene is fused to that of p300 in translocation t(8;22)(p11;q13) (Chaffanet et al, 2000;Kitabayashi et al, 2001b). Moreover, in t(10;16)(q22;p13) associated with childhood AML or therapeutic myelodysplastic syndromes, the MORF gene on 10q22 (Champagne et al, 1999) is fused to that of CBP (Panagopoulos et al, 2001;Kojima et al, 2003).…”

Males absent on the first (MOF): from flies to humans

“…Recent biochemical purifications revealed that both the Drosophila and mammalian MOF proteins reside in multi-protein complexes and that most of these interacting proteins are conserved between Drosophila and mammals (Table 2; Dou et al, 2005;Smith et al, 2005;Mendjan et al, 2006). Co-purification of four human MSL proteins (hMSL1, hMSL2, hMSL3 and hMOF) showed that the MSL (Borrow et al, 1996;Carapeti et al, 1998;Champagne et al, 1999Champagne et al, , 2001Chaffanet et al, 2000;Kitabayashi et al, 2001;Pelletier et al, 2002;Bristow and Shore, 2003;Deguchi et al, 2003;Kindle et al, 2005;Katsumoto et al, 2006;Thomas et al, 2006;Ohta et al, 2007 Abbreviation: HAT, histone acetyltransferases.…”

EP300 (E1A binding protein p300)

“…1::8p11.2→8q13::8q22→8qter),add(19)(p13.3) (Kitabayashi et al, 2001;Tasaka et al, 2002). Hybrid/Mutated gene Monocytic leukemia zinc finger gene (MOZ, Gene EP300 (E1A binding protein p300) Negri G, Gervasini C Atlas Genet Cytogenet Oncol Haematol.…”

“…All MOZ fusion partner genes are involved in histone modification and transcriptional regulation (Katsumoto et al, 2008). To date, only three cases of t(8;22)(p11;q13) involving MOZ and EP300 have been reported and investigated at DNA and RNA levels in two of them (Lai et al, 1992;Soenen et al, 1996;Chaffanet et al, 2000;Kitabayashi et al, 2001;Tasaka et al, 2002). In Chaffanet et al, and in Kitabayashi et al, MOZ-EP300 fusion genes result from the hybrid junction between exon 16 and exon 15 of MOZ with exons 2 and 3 of EP300, respectively.…”