A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression.
J Leukoc Biol
; 70(5): 812-20, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11698502
ABSTRACT
The c-fms gene encodes the receptor for macrophage colony-stimulating factor-1. This gene is expressed selectively in the macrophage cell lineage. Previous studies have implicated sequences in intron 2 that control transcript elongation in tissue-specific and regulated expression of c-fms. Four macrophage-specific deoxyribonuclease I (DNase I)-hypersensitive sites (DHSs) were identified within mouse intron 2. Sequences of these DHSs were found to be highly conserved compared with those in the human gene. A 250-bp region we refer to as the fms intronic regulatory element (FIRE), which is even more highly conserved than the c-fms proximal promoter, contains many consensus binding sites for macrophage-expressed transcription factors including Sp1, PU.1, and C/EBP. FIRE was found to act as a macrophage-specific enhancer and as a promoter with an antisense orientation preference in transient transfections. In stable transfections of the macrophage line RAW264, as well as in clones selected for high- and low-level c-fms mRNA expression, the presence of intron 2 increased the frequency and level of expression of reporter genes compared with those attained using the promoter alone. Removal of FIRE abolished reporter gene expression, revealing a suppressive activity in the remaining intronic sequences. Hence, FIRE is shown to be a key regulatory element in the fms gene.
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Base de dados:
MEDLINE
Assunto principal:
Íntrons
/
Regulação da Expressão Gênica
/
Genes fms
/
Elementos Facilitadores Genéticos
/
Regiões Promotoras Genéticas
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Receptor de Fator Estimulador de Colônias de Macrófagos
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article