title: The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.
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.
authors.affiliation: Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: J
authors.initials: J
authors.lastname: Borrow
authors.forename: V P
authors.initials: VP
authors.lastname: Stanton
authors.forename: J M
authors.initials: JM
authors.lastname: Andresen
authors.forename: R
authors.initials: R
authors.lastname: Becher
authors.forename: F G
authors.initials: FG
authors.lastname: Behm
authors.forename: R S
authors.initials: RS
authors.lastname: Chaganti
authors.forename: C I
authors.initials: CI
authors.lastname: Civin
authors.forename: C
authors.initials: C
authors.lastname: Disteche
authors.forename: I
authors.initials: I
authors.lastname: Dubé
authors.forename: A M
authors.initials: AM
authors.lastname: Frischauf
authors.forename: D
authors.initials: D
authors.lastname: Horsman
authors.forename: F
authors.initials: F
authors.lastname: Mitelman
authors.forename: S
authors.initials: S
authors.lastname: Volinia
authors.forename: A E
authors.initials: AE
authors.lastname: Watmore
authors.forename: D E
authors.initials: DE
authors.lastname: Housman
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050882:CREB-Binding Protein; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D006224:Cricetinae; D015870:Gene Expression; D051548:Histone Acetyltransferases; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics*; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C108712:KAT6A protein, human