Dynamic gene regulation by nuclear colony-stimulating factor 1 receptor in human monocytes and macrophages
| Autor: | Bencheikh, Laura, Diop, M’Boyba Khadija, Rivière, Julie, Imanci, Aygun, Pierron, Gerard, Souquere, Sylvie, Naimo, Audrey, Morabito, Margot, Dussiot, Michaël, De Leeuw, Frédéric, Lobry, Camille, Solary, Eric, Droin, Nathalie |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
THP-1 Cells
Science Primary Cell Culture Article Histones Maleimides Humans RNA Small Interfering lcsh:Science YY1 Transcription Factor Early Growth Response Protein 1 Fluorescent Dyes ets-Domain Protein Elk-1 Gene Editing Macrophage Colony-Stimulating Factor Macrophages Cell Membrane Leukemia Myelomonocytic Chronic Chromatin Gene regulation Gene regulation in immune cells HEK293 Cells Gene Expression Regulation Receptors Granulocyte-Macrophage Colony-Stimulating Factor lcsh:Q Gene expression CRISPR-Cas Systems Transcription Protein Binding Signal Transduction |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Receptor tyrosine kinases localize to the cell surface and have been suggested to also have nuclear function. Here the authors provide evidence that Colony Stimulating Factor-1 Receptor (CSF-1R) migrates to the nucleus upon CSF-1 stimulation in monocytes and that upon differentiation into macrophages, CSF-1R localizes to TSS, co-localizes with H3K4me3, and interacts with ELK and YY1. |
| Databáze: | OpenAIRE |
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