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Interaction and functional cooperation of the leukemia‐associated factors AML1 and p300 in myeloid cell differentiation
Author(s) -
Kitabayashi Issay,
Yokoyama Akihiko,
Shimizu Kimiko,
Ohki Misao
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.11.2994
Subject(s) - biology , myeloid leukemia , myeloid , leukemia , cellular differentiation , genetics , cancer research , computational biology , microbiology and biotechnology , gene
The AML1 transcription factor and the transcriptional coactivators p300 and CBP are the targets of chromosome translocations associated with acute myeloid leukemia and myelodysplastic syndrome. In the t(8;21) translocation, the AML1 ( CBFA2 / PEBP2αB ) gene becomes fused to the MTG8 ( ETO ) gene. We previously found that the terminal differentiation step leading to mature neutrophils in response to granulocyte colony‐stimulating factor (G‐CSF) was inhibited by the ectopic expression of the AML1–MTG8 fusion protein in L‐G murine myeloid progenitor cells. We show here that overexpression of normal AML1 proteins reverses this inhibition and restores the competence to differentiate. Immunoprecipitation analysis shows that p300 and CREB‐binding protein (CBP) interact with AML1. The C‐terminal region of AML1 is responsible for the induction of cell differentiation and for the interaction with p300. Overexpression of p300 stimulates AML1‐dependent transcription and the induction of cell differentiation. These results suggest that p300 plays critical roles in AML1‐dependent transcription during the differentiation of myeloid cells. Thus, AML1 and its associated factors p300 and CBFβ, all of which are targets of chromosomal rearrangements in human leukemia, function cooperatively in the differentiation of myeloid cells.