The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation

The TRAP220 subunit of the thyroid hormone receptor‐associated polypeptide transcription coactivator complex (TRAP/Mediator complex), mammalian counterpart of the yeast Mediator complex, is proposed to act on a variety of major and specific biological events through physical interactions with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220 in nuclear receptor‐mediated monopoiesis and granulopoiesis. The mouse Trap220−/– yolk sac hematopoietic progenitor cells were resistant to 1,25‐dihydroxyvitamin D3‐stimulated differentiation into monocytes/macrophages. Furthermore, flow cytometric analyses showed that HL‐60 cells, human promyelocytic leukemia cell line, wherein TRAP220 was down‐regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25‐dihydroxyvitamin D3 and all‐trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells. These results indicated a crucial role of TRAP220 in the optimal VDR‐ and RAR‐mediated myelomonocytic differentiation processes in mammalian hematopoiesis.

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