Dynamic gene regulation by nuclear colony-stimulating factor 1 receptor in human monocytes and macrophages.
Nat Commun
; 10(1): 1935, 2019 04 26.
Article
em En
| MEDLINE
| ID: mdl-31028249
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mielomonocítica Crônica
/
Regulação da Expressão Gênica
/
Fator Estimulador de Colônias de Macrófagos
/
Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2019
Tipo de documento:
Article