Premium
A highly conserved c‐ fms gene intronic element controls macrophage‐specific and regulated expression
Author(s) -
Himes S. Roy,
Tagoh Hiromi,
Goonetilleke Nilukshi,
Sasmono Tedjo,
Oceandy Delvac,
Clark Richard,
Bonifer Constanze,
Hume David A.
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.5.812
Subject(s) - biology , intron , gene , microbiology and biotechnology , enhancer , gene expression , regulation of gene expression , regulatory sequence , reporter gene , promoter , dnase i hypersensitive site , deoxyribonuclease i , transcription (linguistics) , genetics , linguistics , philosophy , base sequence
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.