The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein.
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.
Borrow
J
J
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Stanton
V P
VP
Andresen
J M
JM
Becher
R
R
Behm
F G
FG
Chaganti
R S
RS
Civin
C I
CI
Disteche
C
C
Dubé
I
I
Frischauf
A M
AM
Horsman
D
D
Mitelman
F
F
Volinia
S
S
Watmore
A E
AE
Housman
D E
DE
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
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