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 CBP. 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetyltransferases / genetics*
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Amino Acid Sequence
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Animals
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Base Sequence
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CREB-Binding Protein
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Chromosome Mapping
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Chromosomes, Human, Pair 16*
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Chromosomes, Human, Pair 8*
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Cloning, Molecular
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Cricetinae
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Gene Expression
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Histone Acetyltransferases
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Humans
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Leukemia, Monocytic, Acute / genetics*
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Leukemia, Myelomonocytic, Acute / genetics*
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Molecular Sequence Data
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Nuclear Proteins / genetics*
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Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Trans-Activators*
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Transcription Factors / genetics*
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Translocation, Genetic*
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Zinc Fingers / genetics
Substances
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Nuclear Proteins
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Trans-Activators
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Transcription Factors
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Acetyltransferases
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CREB-Binding Protein
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CREBBP protein, human
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Histone Acetyltransferases
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KAT6A protein, human
Associated data
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GENBANK/AF012283
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GENBANK/U47741
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GENBANK/U47742