A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor
A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor
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组蛋白伴侣 DEK 在转录上共激活核受体
DOI：
10.1101/gad.1857410
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发表时间：
2010-01-15
影响因子：
10.5
通讯作者：
Kato, Shigeaki
中科院分区：
文献类型：
--
作者：
Sawatsubashi, Shun;Murata, Takuya;Kato, Shigeaki
染色质重组对于序列特异性转录因子的转录调控至关重要。然而，转录调控和染色质重组之间的分子联系仍不清楚。通过将蜕皮激素受体(ECR)共定位于蜕皮激素诱导的唾液腺肿胀上，果蝇Ddek(Ddek)在昆虫细胞和正常果蝇中都被鉴定为ECR的共激活因子。对含有苍蝇和人DEK的复合体的生化纯化和表征表明，DEK通过与酪蛋白激酶2形成复合体，通过磷酸化作为组蛋白伴侣。与DEK复合体与富含活性表观遗传标记的组蛋白优先结合一致，DDEK促进了H3.3在泡芙形成过程中的组装。在一些人类髓系白血病患者中，DEK通过染色体易位与CaN融合。这种突变显著减少了DEK复合体的形成，这是组蛋白伴侣活性所必需的。因此，本研究表明，至少有一个组蛋白伴侣可以被归类为核受体的转录辅助激活因子。
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.