title: Dual regulation of SPI1/PU.1 transcription factor by heat shock factor 1 (HSF1) during macrophage differentiation of monocytes.
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.
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: G
authors: G
authors: Jego
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: D
authors: D
authors: Lanneau
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: A
authors: A
authors: De Thonel
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: K
authors: K
authors: Berthenet
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: A
authors: A
authors: Hazoumé
authors: 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.
authors: N
authors: N
authors: Droin
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: A
authors: A
authors: Hamman
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: F
authors: F
authors: Girodon
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: P-S
authors: PS
authors: Bellaye
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: G
authors: G
authors: Wettstein
authors: 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.
authors: A
authors: A
authors: Jacquel
authors: 1] Faculty of Medicine and Pharmacy, Génétique et anomalies du développement, University of Burgundy, Dijon, France [2] CHU, Dijon, France.
authors: L
authors: L
authors: Duplomb
authors: 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.
authors: A
authors: A
authors: Le Mouël
authors: University Paris Diderot, Sorbonne Paris Cité, Institut jacques Monod, UMR 7592, Paris cedex 13, France.
authors: C
authors: C
authors: Papanayotou
authors: CNRS, UMR 5547, Université Paul Sabatier, 118 route de Narbonne, Toulouse, France.
authors: E
authors: E
authors: Christians
authors: 1] INSERM, UMR 866, 'Equipe Labellisée Ligue contre le Cancer', Dijon, France [2] Faculty of Medicine and Pharmacy, University of Burgundy, Dijon, France.
authors: P
authors: P
authors: Bonniaud
authors: 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.
authors: V
authors: V
authors: Lallemand-Mezger
authors: 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.
authors: E
authors: E
authors: Solary
authors: 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.
authors: C
authors: C
authors: Garrido
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006801:Humans; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000032:analysis; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*; D000098902:CD163 Antigen; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D014157:Transcription Factors; D000098902:CD163 Antigen; D000099232:Proto-Oncogene Protein Spi-1; C000619706:HSF1 protein, human