The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus

Research output: Contribution to journalArticle

Authors

  • Kristin A Sauter
  • M Amine Bouhlel
  • Julie O'Neal
  • David P Sester
  • Hiromi Tagoh
  • Richard M Ingram
  • Clare Pridans
  • David A Hume

Colleges, School and Institutes

Abstract

The gene encoding the receptor for macrophage colony-stimulating factor (CSF-1R) is expressed exclusively in cells of the myeloid lineages as well as trophoblasts. A conserved element in the second intron, Fms-Intronic Regulatory Element (FIRE), is essential for macrophage-specific transcription of the gene. However, the molecular details of how FIRE activity is regulated and how it impacts the Csf1r promoter have not been characterised. Here we show that agents that down-modulate Csf1r mRNA transcription regulated promoter activity altered the occupancy of key FIRE cis-acting elements including RUNX1, AP1, and Sp1 binding sites. We demonstrate that FIRE acts as an anti-sense promoter in macrophages and reversal of FIRE orientation within its native context greatly reduced enhancer activity in macrophages. Mutation of transcription initiation sites within FIRE also reduced transcription. These results demonstrate that FIRE is an orientation-specific transcribed enhancer element.

Details

Original languageEnglish
Pages (from-to)e54935
JournalPLoS ONE
Volume8
Issue number1
Publication statusPublished - 2013

Keywords

  • Animals, Base Sequence, Binding Sites, Conserved Sequence, Down-Regulation, Gene Expression Regulation, Enzymologic, Genetic Loci, Humans, Introns, Lipopolysaccharides, Macrophage Colony-Stimulating Factor, Macrophages, Mice, Molecular Sequence Data, RNA Polymerase II, RNA, Antisense, RNA, Messenger, Receptor, Macrophage Colony-Stimulating Factor, Regulatory Sequences, Nucleic Acid, Sp1 Transcription Factor, Time Factors, Transcription Factor AP-1