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 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.
Urahama
Norinaga
N
Division of Hematology/Oncology, Department of Medicine, Kobe University School of Medicine, Japan.
Ito
Mitsuhiro
M
Sada
Akiko
A
Yakushijin
Kimikazu
K
Yamamoto
Katsuya
K
Okamura
Atsuo
A
Minagawa
Kentaro
K
Hato
Akio
A
Chihara
Kazuo
K
Roeder
Robert G
RG
Matsui
Toshimitsu
T
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D042381:Granulocyte Precursor Cells / Q000502:physiology*; D018922:HL-60 Cells; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D056913:Mediator Complex Subunit 1; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018167:Receptors, Calcitriol / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology
D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; C538855:MED1 protein, human; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D014212:Tretinoin