Functional analysis of the murine Emr1 promoter identifies a novel purine-rich regulatory motif required for high-level gene expression in macrophages.
This study has investigated the transcriptional regulation of the Emr1 gene in murine macrophages and defined an enhancer element within the proximal promoter that is necessary for Emr1 expression in myeloid cells. This element consists of an extended purine-rich sequence (PuRS) of 83 consecutive purine residues containing 9 GGAA sequences, the core binding sequence for members of the Ets family of transcription factors. The Ets factor PU.1 associates with this PuRS element both in vitro and in vivo. Using a standard BLAST search we identified similar PuRS elements in other myeloid and nonmyeloid genes. All PuRS elements tested confer enhancer activity onto a heterologous promoter and chromatin immunoprecipitation experiments revealed that PU.1 associates in vivo with the PuRS elements from the genes expressed in myeloid cells. Our results provide evidence that extended purine-rich sequence elements may constitute a new transcription regulatory motif and that PU.1 association is a prerequisite for macrophage-specific expression.
O'Reilly
Dawn
D
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Addley
Mark
M
Quinn
Carmel
C
MacFarlane
Alison J
AJ
Gordon
Siamon
S
McKnight
Andrew J
AJ
Greaves
David R
DR
D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009077:Mucins / Q000235:genetics* / Q000378:metabolism; D022423:Myeloid Cells / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011687:Purines / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D000099232:Proto-Oncogene Protein Spi-1
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009077:Mucins; D011518:Proto-Oncogene Proteins; D011687:Purines; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C094471:ADGRE1 protein, human