4.7 Article

A histone chaperone, DEK, transcriptionally coactivates a nuclear receptor

期刊

GENES & DEVELOPMENT
卷 24, 期 2, 页码 159-170

出版社

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1857410

关键词

DEK; acute myeloid leukemia; histone chaperone; ecdysone receptor; coactivator; histone variant H3.3

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  1. Ministry of Education, Culture, Sports, Science, and Technology of Japan
  2. Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Agency (JST)

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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.

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