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Publication : The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation.

First Author  Urahama N Year  2005
Journal  Genes Cells Volume  10
Issue  12 Pages  1127-37
PubMed ID  16324150 Mgi Jnum  J:111900
Mgi Id  MGI:3655015 Doi  10.1111/j.1365-2443.2005.00906.x
Citation  Urahama N, et al. (2005) The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation. Genes Cells 10(12):1127-37
abstractText  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 D(3)-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 D(3) 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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