The interleukin-8 receptors (CXCR1 and CXCR2) are specifically expressed at high levels in cells of the neutrophil lineage. In this work we identify promoter elements of the CXCR1 gene and the ets family transcription factor PU.1 as a major regulator for activation of the CXCR1 promoter. We first showed that the upstream sequence of CXCR1 (-800 to +86 base pairs (bp)) directs myeloid-specific expression of reporter gene constructs. Second, we showed the presence of negative elements in the sequence from -800 to -128 bp and positive elements from -128 to + 50 bp. Third, we demonstrated that the fragment -22 to +14 bp binds PU. 1. Fourth, we showed that PU.1 transactivates the CXCR1 promoter. These data are the first demonstration of PU.1-mediated transcriptional regulation of a neutrophil chemoattractant G protein-coupled receptor.
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