The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein

Nat Genet. 1996 Sep;14(1):33-41. doi: 10.1038/ng0996-33.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetyltransferases / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • CREB-Binding Protein
  • Chromosome Mapping
  • Chromosomes, Human, Pair 16*
  • Chromosomes, Human, Pair 8*
  • Cloning, Molecular
  • Cricetinae
  • Gene Expression
  • Histone Acetyltransferases
  • Humans
  • Leukemia, Monocytic, Acute / genetics*
  • Leukemia, Myelomonocytic, Acute / genetics*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factors / genetics*
  • Translocation, Genetic*
  • Zinc Fingers / genetics

Substances

  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • KAT6A protein, human

Associated data

  • GENBANK/AF012283
  • GENBANK/U47741
  • GENBANK/U47742