A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression

Research output: Contribution to journalArticlepeer-review

Authors

  • SR Himes
  • H Tagoh
  • N Goonetilleke
  • T Sasmono
  • D Oceandy
  • R Clark
  • DA Hume

Colleges, School and Institutes

Abstract

The c fins 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 fins intronic regulatory element (FIRE), which is even more highly conserved than the c-fins proximal promoter, contains many consensus binding sites for macrophage-expressed transcription factors including Spl, 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 fins gene.

Details

Original languageEnglish
Pages (from-to)812-820
Number of pages9
JournalJournal of Leukocyte Biology
Volume70
Issue number5
Publication statusPublished - 1 Nov 2001

Keywords

  • enhancer, DNase 1hypersensitivity, intron, transcription