2. Academic Validation
  3. Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes

Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes

  • Leukemia. 2014 Aug;28(8):1676-86. doi: 10.1038/leu.2014.63.
G Jego 1,  D Lanneau 1,  A De Thonel 1,  K Berthenet 1,  A Hazoumé 1,  N Droin 2,  A Hamman 1,  F Girodon 1,  P-S Bellaye 1,  G Wettstein 1,  A Jacquel 3,  L Duplomb 4,  A Le Mouël 5,  C Papanayotou 6,  E Christians 7,  P Bonniaud 1,  V Lallemand-Mezger 5,  E Solary 2,  C Garrido 8
Affiliations

Affiliations

  • 1 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
  • 2 1] INSERM, UMR 1009, Institut Gustave Roussy, 114 rue Edouard Vaillaint, Villejuif, France [2] University Paris-Sud 11, Institut Gustave Roussy, 114 rue Edouard Vaillaint, Villejuif, France.
  • 3 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France [3] INSERM, U526, Nice, France.
  • 4 1] Faculty of Medicine and Pharmacy, Génétique et anomalies du développement, University of Burgundy, Dijon, France [2] CHU, Dijon, France.
  • 5 1] CNRS, UMR7216 Épigénétique et Destin Cellulaire, 35 rue Hélène Brion, Paris, France [2] University Paris Diderot, Sorbonne Paris Cité, 35 rue Hélène Brion, Paris, France.
  • 6 University Paris Diderot, Sorbonne Paris Cité, Institut jacques Monod, UMR 7592, Paris cedex 13, France.
  • 7 CNRS, UMR 5547, Université Paul Sabatier, 118 route de Narbonne, Toulouse, France.
  • 8 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France [3] Centre de lutte contre le cancer George-François Leclerc, Dijon, France.
PMID: 24504023 DOI: 10.1038/leu.2014.63
Abstract

In addition to their cytoprotective role in stressful conditions, heat shock proteins (HSPs) are involved in specific differentiation pathways, for example, we have identified a role for HSP90 in macrophage differentiation of human peripheral blood monocytes that are exposed to macrophage colony-stimulating factor (M-CSF). Here, we show that deletion of the main transcription factor involved in heat shock gene regulation, heat shock factor 1 (HSF1), affects M-CSF-driven differentiation of mouse bone marrow cells. HSF1 transiently accumulates in the nucleus of human monocytes undergoing macrophage differentiation, including M-CSF-treated peripheral blood monocytes and phorbol ester-treated THP1 cells. We demonstrate that HSF1 has a dual effect on SPI1/PU.1, a transcription factor essential for macrophage differentiation and whose deregulation can lead to the development of leukemias and lymphomas. Firstly, HSF1 regulates SPI1/PU.1 gene expression through its binding to a heat shock element within the intron 2 of this gene. Furthermore, downregulation or inhibition of HSF1 impaired both SPI1/PU.1-targeted gene transcription and macrophage differentiation. Secondly, HSF1 induces the expression of HSP70 that interacts with SPI1/PU.1 to protect the transcription factor from proteasomal degradation. Taken together, HSF1 appears as a fine-tuning regulator of SPI1/PU.1 expression at the transcriptional and post-translational levels during macrophage differentiation of monocytes.

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