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The role of transcriptional coactivator TRAP220 in myelomonocytic differentiation

Norinaga Urahama1, Mitsuhiro Ito, Akiko Sada

  • 1Division of Hematology/Oncology, Department of Medicine, Kobe University School of Medicine, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|December 6, 2005
PubMed

Insights

TRAP220 is crucial for myeloid differentiation. This study shows TRAP220 enables vitamin D receptor (VDR) and retinoic acid receptor (RAR) to effectively promote monocyte and granulocyte development.

Area of Science:

  • Molecular Biology
  • Hematopoiesis
  • Cell Differentiation

Background:

  • TRAP220 is a subunit of the TRAP/Mediator complex, interacting with nuclear receptors.
  • Nuclear receptors like VDR and RAR are vital for monopoiesis and granulopoiesis.

Purpose of the Study:

  • To investigate the functional role of TRAP220 in nuclear receptor-mediated monopoiesis and granulopoiesis.
  • To elucidate TRAP220's contribution to VDR- and RAR-driven myeloid differentiation.

Main Methods:

  • Analysis of mouse Trap220(-/-) yolk sac hematopoietic progenitor cells.
  • Flow cytometry and gene expression analysis in HL-60 cells with TRAP220 knockdown.
  • Stimulation with 1,25-dihydroxyvitamin D(3) and all-trans retinoic acid.

Main Results:

  • Trap220(-/-) progenitor cells showed resistance to VDR-stimulated differentiation.
  • TRAP220 knockdown in HL-60 cells impaired differentiation into monocytes and granulocytes.
  • Expression of VDR/RAR target genes and differentiation markers was reduced in knockdown cells.

Conclusions:

  • TRAP220 plays a critical role in VDR- and RAR-mediated myelomonocytic differentiation.
  • TRAP220 is essential for optimal mammalian hematopoiesis involving these nuclear receptors.

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