Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1

<p>Abstract</p> <p>Background</p> <p>CC Chemokine Receptor 3 (CCR3), the major chemokine receptor expressed on eosinophils, binds promiscuously to several ligands including eotaxins 1, 2, and 3. Even though the only cells that consistently accumulate following eotaxin a...

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Bibliographic Details
Main Authors: Koch Laura E, Colyer Jessica L, Zimmermann Nives, Rothenberg Marc E
Format: Article
Language:English
Published: BMC 2005-04-01
Series:BMC Immunology
Online Access:http://www.biomedcentral.com/1471-2172/6/7
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Summary:<p>Abstract</p> <p>Background</p> <p>CC Chemokine Receptor 3 (CCR3), the major chemokine receptor expressed on eosinophils, binds promiscuously to several ligands including eotaxins 1, 2, and 3. Even though the only cells that consistently accumulate following eotaxin administration <it>in vivo </it>are myeloid cells (primarily eosinophils), other cell types have recently been shown to express CCR3. It is therefore important to elucidate the molecular mechanisms regulating receptor expression.</p> <p>Results</p> <p>In order to define regions responsible for CCR3 transcription, a DNAse hypersensitive site was identified in the vicinity of exon 1. Coupled with our previous data implicating exon 1 in CCR3 transcription, we hypothesized that transcription factors bind to exon-1. Electrophoretic mobility shift analysis revealed that nuclear proteins in eosinophilic cells bound to exon 1. Furthermore, antibody interference and mutation studies demonstrated GATA-1 binding to exon 1. In order to test the 1.6-kb CCR3 promoter element (that includes exon 1) for <it>in vivo </it>function, this region was used to generate transgenic mice that expressed a reporter protein. Strong transgene expression was achieved, with the pattern of expression suggesting a broad acting promoter.</p> <p>Conclusion</p> <p>The transcription factor GATA-1 binds to CCR3 exon 1. The 1.6-kb CCR3 promoter element, that includes exon 1, is a strong promoter <it>in vivo</it>.</p>
ISSN:1471-2172