| Abstract: |
The recurrent translocation t(8;16)(p11;p13) is a cytogenetic hallmark for the M4/M5 subtype of acute myeloid leukaemia. Here we identify the breakpoint-associated genes. Positional cloning on chromosome 16 implicates the CREB-binding protein (CBP), a transcriptional adaptor/coactivator protein. At the chromosome 8 breakpoint we identify a novel gene, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature. In-frame MOZ-CBP fusion transcripts combine the MOZ finger motifs and putative acetyltransferase domain with a largely intact CBR. We suggest that MOZ may represent a chromatin-associated acetyltransferase, and raise the possibility that a dominant MOZ-CBP fusion protein could mediate leukaemogenesis via aberrant chromatin acetylation. |
| Keywords: |
acute granulocytic leukemia; gene translocation; polymerase chain reaction; animals; gene expression; cytogenetics; chromosomes, human, pair 8; transcription factors; nuclear proteins; molecular cloning; cloning, molecular; amino acid sequence; molecular sequence data; sequence homology, amino acid; hybrid protein; chromatin; leukemogenesis; base sequence; translocation, genetic; trans-activators; zinc finger protein; acyltransferase; acetyltransferases; acetylation; chromosome mapping; cyclic amp responsive element binding protein; cricetinae; zinc fingers; chromosomes, human, pair 16; leukemia, monocytic, acute; chromosome translocation 8; creb-binding protein; histone acetyltransferases; humans; priority journal; article; chromosome translocation 16; leukemia, myelomonocytic, acute
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