Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1

Scott A. Wegner, Philip K. Ehrenberg, George Chang, Deborah E. Dayhoff, Alex L. Sleeker, Nelson L. Michael*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

CXCR4 is both a chemokine receptor and entry coreceptor for T-cell line- adapted human immunodeficiency virus type 1. The genomic organization and promoter function for the entire transcription unit of CXCR4 were determined. The gene contains 2 exons of 103 and 1563 base pairs (bp) interrupted by a 2132-bp intron precisely between codons 5 and 6 of the coding sequences. A transcription start site was identified 88 bp upstream of the initiation codon, and a polyadenylate addition site was identified 22 bp 3' to a polyadenylation signal. Transient expression assays defined a minimal promoter at positions -114 to +43 relative to the transcription start site. This region contains a TATA box, a nuclear respiratory factor-1 (NRF-1) site, and two GC boxes. Specific factor binding to the NRF-1 site and GC boxes were demonstrated by gel mobility shifts and DNase I footprinting. Site-directed mutagenesis showed that the NRF-1 site is crucial for promoter activity providing the first evidence for the regulation of a signal transduction gene by NRF-1. Sequences between -691 and -191 repress CXCR4 promoter activity. Further study of these regulatory elements will be important to understanding how CXCR4 functions as both a chemokine receptor and human immunodeficiency virus type 1 entry co-receptor.

Original languageEnglish
Pages (from-to)4754-4760
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number8
DOIs
StatePublished - 20 Feb 1998
Externally publishedYes

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