Abstract
The proto-oncogene protein DEK has been implicated in the t(6;9) chromosomal translocation associated with a subtype of acute myelogenous leukemia (AML), which results in the formation of a DEK-CAN fusion protein. Histone acetylation is an important post-translational modification which is involved in transcriptional regulation. In this study, we report that the acidic domain containing protein DEK interacts with histones and exerts a potent inhibitory effect on both p300 and PCAF-mediated histone acetyltransferase activity and transcription. Using chromatin immunoprecipitation assays, we have demonstrated that the recruitment of DEK to the appropriate promoter induces the histone H3 and H4 hypoacetylation of chromatin. Collectively, our data illustrate the important regulatory role played by protein DEK in transcriptional regulation, and suggest that transcription-regulating acidic domain regions may play a role in leukemogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Cell Cycle Proteins / antagonists & inhibitors*
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Cell Cycle Proteins / genetics
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Chromatin / metabolism
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism*
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E1A-Associated p300 Protein / antagonists & inhibitors*
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E1A-Associated p300 Protein / genetics
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Gene Expression Regulation, Enzymologic
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Histone Acetyltransferases / antagonists & inhibitors*
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Histone Acetyltransferases / genetics
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Histones / metabolism
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Humans
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Immunoprecipitation
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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Poly-ADP-Ribose Binding Proteins
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Promoter Regions, Genetic
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Protein Interaction Mapping
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Protein Structure, Tertiary
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Proto-Oncogene Mas
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / genetics
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p300-CBP Transcription Factors
Substances
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Cell Cycle Proteins
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Chromatin
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Chromosomal Proteins, Non-Histone
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DEK protein, human
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Histones
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MAS1 protein, human
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Oncogene Proteins
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Poly-ADP-Ribose Binding Proteins
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Proto-Oncogene Mas
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Transcription Factors
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E1A-Associated p300 Protein
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EP300 protein, human
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor