A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor

被引:118
作者
Sawatsubashi, Shun [1 ,2 ]
Murata, Takuya [1 ]
Lim, Jinseon [1 ]
Fujiki, Ryoji [1 ]
Ito, Saya [1 ,2 ]
Suzuki, Eriko [1 ,2 ]
Tanabe, Masahiko [1 ,2 ]
Zhao, Yue [1 ]
Kimura, Shuhei [1 ]
Fujiyama, Sally [1 ,2 ]
Ueda, Takashi [1 ]
Umetsu, Daiki [1 ]
Ito, Takashi [3 ]
Takeyama, Ken-ichi [1 ]
Kato, Shigeaki [1 ,2 ]
机构
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1130032, Japan
[2] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan
[3] Nagasaki Univ, Sch Med, Dept Biochem, Nagasaki 8528523, Japan
基金
日本科学技术振兴机构;
关键词
DEK; acute myeloid leukemia; histone chaperone; ecdysone receptor; coactivator; histone variant H3.3; CHROMATIN-STRUCTURE; ECDYSONE RECEPTOR; TRANSLOCATION; 6-9; GENE-EXPRESSION; IN-VIVO; DROSOPHILA; COMPLEXES; H3.3; PROTEINS; RNA;
D O I
10.1101/gad.1857410
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:159 / 170
页数:12
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