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Differentiation

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

Leukemia volume 28, pages 1676–1686 (2014)Cite this article

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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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Acknowledgements

We thank Dr Moreau-Gachelin and Pr Tenen for providing us the SPI1/PU.1 vectors, A Bouchot and D Sabéran-Djoneidi for excellent technical assistance. CG team belongs to the LabEx LipSTIC. This work was supported by the ‘Investissements d’Avenir’ (ANR-11-LABX-0021), the Ligue Nationale Contre le Cancer (AJ, GC, ES), the Association pour la Recherche sur le Cancer (DL), l’Institut National du Cancer (CG) and FEDER.

Author Contributions

GJ, DL, ADT, ES, CG, designed the study and experiments; GJ, DL, ADT, ND, AH, KB, P-SB, GW, AJ, LD and ALM performed the experiments; VLM, EC, CP, PB and ND provided samples and expertise; GJ, DL, ADT, ND, AH, PB, AH and LD analyzed the experiments; CG directed the work.

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Authors and Affiliations

  1. INSERM, UMR 866, ‘Equipe Labellisée Ligue contre le Cancer’, Dijon, France

    G Jego, D Lanneau, A De Thonel, K Berthenet, A Hazoumé, A Hamman, F Girodon, P-S Bellaye, G Wettstein, A Jacquel, P Bonniaud & C Garrido

  2. Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France

    G Jego, D Lanneau, A De Thonel, K Berthenet, A Hazoumé, A Hamman, F Girodon, P-S Bellaye, G Wettstein, A Jacquel, P Bonniaud & C Garrido

  3. INSERM, UMR 1009, Institut Gustave Roussy, 114 rue Edouard Vaillaint, Villejuif, France

    N Droin & E Solary

  4. University Paris-Sud 11, Institut Gustave Roussy, 114 rue Edouard Vaillaint, Villejuif, France

    N Droin & E Solary

  5. INSERM, U526, Nice, France

    A Jacquel

  6. Faculty of Medicine and Pharmacy, Génétique et anomalies du développement, University of Burgundy, Dijon, France

    L Duplomb

  7. CHU, Dijon, France

    L Duplomb

  8. CNRS, UMR7216 Épigénétique et Destin Cellulaire, 35 rue Hélène Brion, Paris, France

    A Le Mouël & V Lallemand-Mezger

  9. University Paris Diderot, Sorbonne Paris Cité, 35 rue Hélène Brion, Paris, France

    A Le Mouël & V Lallemand-Mezger

  10. University Paris Diderot, Sorbonne Paris Cité, Institut jacques Monod, UMR 7592, Paris cedex 13, France

    C Papanayotou

  11. CNRS, UMR 5547, Université Paul Sabatier, 118 route de Narbonne, Toulouse, France

    E Christians

  12. Centre de lutte contre le cancer George-François Leclerc, Dijon, France

    C Garrido

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  1. G Jego
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Correspondence to C Garrido.

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Jego, G., Lanneau, D., De Thonel, A. et al. Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes. Leukemia 28, 1676–1686 (2014). https://doi.org/10.1038/leu.2014.63

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