Dynamic gene regulation by nuclear colony-stimulating factor 1 receptor in human monocytes and macrophages

Laura Bencheikh, M’Boyba Khadija Diop, Julie Rivière, Aygun Imanci, Gerard Pierron, Sylvie Souquere, Audrey Naimo, Margot Morabito, Michaël Dussiot, Frédéric De Leeuw, Camille Lobry, Eric Solary () and Nathalie Droin ()
Additional contact information
Laura Bencheikh: Gustave Roussy Cancer Center
M’Boyba Khadija Diop: Gustave Roussy Cancer Center
Julie Rivière: Gustave Roussy Cancer Center
Aygun Imanci: Gustave Roussy Cancer Center
Gerard Pierron: Gustave Roussy Cancer Center
Sylvie Souquere: Gustave Roussy Cancer Center
Audrey Naimo: Gustave Roussy Cancer Center
Margot Morabito: Gustave Roussy Cancer Center
Michaël Dussiot: Hôpital Necker Enfants Malades
Frédéric De Leeuw: Gustave Roussy Cancer Center
Camille Lobry: Gustave Roussy Cancer Center
Eric Solary: Gustave Roussy Cancer Center
Nathalie Droin: Gustave Roussy Cancer Center

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Despite their location at the cell surface, several receptor tyrosine kinases (RTK) are also found in the nucleus, as either intracellular domains or full length proteins. However, their potential nuclear functions remain poorly understood. Here we find that a fraction of full length Colony Stimulating Factor-1 Receptor (CSF-1R), an RTK involved in monocyte/macrophage generation, migrates to the nucleus upon CSF-1 stimulation in human primary monocytes. Chromatin-immunoprecipitation identifies the preferential recruitment of CSF-1R to intergenic regions, where it co-localizes with H3K4me1 and interacts with the transcription factor EGR1. When monocytes are differentiated into macrophages with CSF-1, CSF-1R is redirected to transcription starting sites, colocalizes with H3K4me3, and interacts with ELK and YY1 transcription factors. CSF-1R expression and chromatin recruitment is modulated by small molecule CSF-1R inhibitors and altered in monocytes from chronic myelomonocytic leukemia patients. Unraveling this dynamic non-canonical CSF-1R function suggests new avenues to explore the poorly understood functions of this receptor and its ligands.

Date: 2019
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DOI: 10.1038/s41467-019-09970-9

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