Regulation of histone acetyltransferase activity of p300 and PCAF by proto-oncogene protein DEK.
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.
Ko
Soo-Il
SI
Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 156-756, Republic of Korea.
Lee
In-Seon
IS
Kim
Ji-Young
JY
Kim
Sung-Mi
SM
Kim
Dong-Wook
DW
Lee
Kyu-Sun
KS
Woo
Kyung-Mi
KM
Baek
Jeong-Hwa
JH
Choo
Jong-Kil
JK
Seo
Sang-Beom
SB
D000107:Acetylation; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000037:antagonists & inhibitors* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D050881:E1A-Associated p300 Protein; D051548:Histone Acetyltransferases; D006657:Histones; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C084738:DEK protein, human; C000715470:MAS1 protein, human; C494360:EP300 protein, human