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¹ Division of Hematology/Oncology, Department of Medicine, Kobe University School of Medicine,Kobe 650-0017, Japan
² Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
³ Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021-6399, USA

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.

^* Correspondence: E-mail: itomi{at}med.kobe-u.ac.jp

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