TY - JOUR
T1 - The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation
AU - Urahama, Norinaga
AU - Ito, Mitsuhiro
AU - Sada, Akiko
AU - Yakushijin, Kimikazu
AU - Yamamoto, Katsuya
AU - Okamura, Atsuo
AU - Minagawa, Kentaro
AU - Hato, Akio
AU - Chihara, Kazuo
AU - Roeder, Robert G.
AU - Matsui, Toshimitsu
PY - 2005/12
Y1 - 2005/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=29244445499&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2443.2005.00906.x
DO - 10.1111/j.1365-2443.2005.00906.x
M3 - Article
C2 - 16324150
AN - SCOPUS:29244445499
SN - 1356-9597
VL - 10
SP - 1127
EP - 1137
JO - Genes to Cells
JF - Genes to Cells
IS - 12
ER -