title: The function of the conserved regulatory element within the second intron of the mammalian Csf1r locus.
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.
authors: Developmental Biology, The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, United Kingdom.
authors: Kristin A
authors: KA
authors: Sauter
authors: M Amine
authors: MA
authors: Bouhlel
authors: Julie
authors: J
authors: O'Neal
authors: David P
authors: DP
authors: Sester
authors: Hiromi
authors: H
authors: Tagoh
authors: Richard M
authors: RM
authors: Ingram
authors: Clare
authors: C
authors: Pridans
authors: Constanze
authors: C
authors: Bonifer
authors: David A
authors: DA
authors: Hume
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D056426:Genetic Loci / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000187:drug effects / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D012319:RNA Polymerase II / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016372:RNA, Antisense; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D018808:Transcription Factor AP-1; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor; D012319:RNA Polymerase II
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