A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor.
Chromatin reorganization is essential for transcriptional control by sequence-specific transcription factors. However, the molecular link between transcriptional control and chromatin reconfiguration remains unclear. By colocalization of the nuclear ecdysone receptor (EcR) on the ecdysone-induced puff in the salivary gland, Drosophila DEK (dDEK) was genetically identified as a coactivator of EcR in both insect cells and intact flies. Biochemical purification and characterization of the complexes containing fly and human DEKs revealed that DEKs serve as histone chaperones via phosphorylation by forming complexes with casein kinase 2. Consistent with the preferential association of the DEK complex with histones enriched in active epigenetic marks, dDEK facilitated H3.3 assembly during puff formation. In some human myeloid leukemia patients, DEK was fused to CAN by chromosomal translocation. This mutation significantly reduced formation of the DEK complex, which is required for histone chaperone activity. Thus, the present study suggests that at least one histone chaperone can be categorized as a type of transcriptional coactivator for nuclear receptors.
Sawatsubashi
Shun
S
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
Murata
Takuya
T
Lim
Jinseon
J
Fujiki
Ryoji
R
Ito
Saya
S
Suzuki
Eriko
E
Tanabe
Masahiko
M
Zhao
Yue
Y
Kimura
Shuhei
S
Fujiyama
Sally
S
Ueda
Takashi
T
Umetsu
Daiki
D
Ito
Takashi
T
Takeyama
Ken-ichi
K
Kato
Shigeaki
S
D000818:Animals; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism; D019143:Evolution, Molecular; D056488:Histone Chaperones / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology; D009707:Nucleosomes / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D029721:Drosophila Proteins; D056488:Histone Chaperones; D009707:Nucleosomes; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D004440:Ecdysone; C119557:Dek protein, Drosophila; D036081:Receptors, Eph Family