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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
38
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pubmed:dateCreated |
2003-9-15
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pubmed:abstractText |
Murine Nramp1 encodes a divalent cation transporter that is expressed in late endosomes/lysosomes of macrophages, and the transported cations facilitate intracellular pathogen growth control. The Nramp1 promoter is TATA box-deficient, has two initiator elements, and is repressed by c-Myc, in accordance with the notion that genes that deplete the iron content of the cell cytosol antagonize cell growth. Repression via c-Myc occurs at the initiator elements, whereas a c-Myc-interacting protein (Miz-1) stimulates transcription. Here we demonstrate that a non-canonical E box (CAACTG) inhibits basal promoter activity and activation by Miz-1. A consensus Sp1-binding site or GC box is also necessary for Miz-1-dependent transactivation, but not repression. Repression occurs by c-Myc competing with p300/CBP for binding Miz-1. Our results show that an Sp1 site mutant inhibits coactivation by p300 and that the murine Nramp1 promoter is preferentially expressed within macrophages (relative to a beta-actin control) compared with non-macrophage cells. The effect of the Sp1 site mutation on promoter function shows cell-type specificity: stimulation in COS-1 and inhibition in RAW264.7 cells. Miz-1-directed RNA interference confirms a stimulatory role for Miz-1 in Nramp1 promoter function. c-Myc, Miz-1, and Sp1 were identified as binding to the Nramp1 core promoter in control cells and following acute stimulation with interferon-gamma and lipopolysaccharide. These results provide a description of sites that modulate the activity of the initiator-binding protein Miz-1 and indicate a stimulatory role for GC box-binding factors in macrophages and a inhibitory role for E box elements in proliferating cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36017-26
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12840021-Animals,
pubmed-meshheading:12840021-Binding Sites,
pubmed-meshheading:12840021-COS Cells,
pubmed-meshheading:12840021-Cation Transport Proteins,
pubmed-meshheading:12840021-Cations,
pubmed-meshheading:12840021-Cell Division,
pubmed-meshheading:12840021-Chromatin,
pubmed-meshheading:12840021-DNA-Binding Proteins,
pubmed-meshheading:12840021-Dose-Response Relationship, Drug,
pubmed-meshheading:12840021-Gene Deletion,
pubmed-meshheading:12840021-Genes, Reporter,
pubmed-meshheading:12840021-Interferon-gamma,
pubmed-meshheading:12840021-Iron,
pubmed-meshheading:12840021-Lipopolysaccharides,
pubmed-meshheading:12840021-Macrophages,
pubmed-meshheading:12840021-Mice,
pubmed-meshheading:12840021-Mice, Inbred C57BL,
pubmed-meshheading:12840021-Models, Genetic,
pubmed-meshheading:12840021-Mutation,
pubmed-meshheading:12840021-Plasmids,
pubmed-meshheading:12840021-Precipitin Tests,
pubmed-meshheading:12840021-Promoter Regions, Genetic,
pubmed-meshheading:12840021-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:12840021-RNA Interference,
pubmed-meshheading:12840021-Sp1 Transcription Factor,
pubmed-meshheading:12840021-Transcription, Genetic,
pubmed-meshheading:12840021-Transcriptional Activation,
pubmed-meshheading:12840021-Transfection,
pubmed-meshheading:12840021-Zinc Fingers
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pubmed:year |
2003
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pubmed:articleTitle |
Characterization of the murine Nramp1 promoter: requirements for transactivation by Miz-1.
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pubmed:affiliation |
Division of Biochemistry and Molecular Biology, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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