1. ¹INSERM, U976, Paris, France
2. ²Université Paris 12, Faculté de Médecine, Créteil, France

Correspondence: Dr C Schmitt, Inserm U976, Pavillon Bazin, Hôpital St-Louis, 1 avenue Claude Vellefaux, 75475 Paris, France. E-mail: christian.schmitt@inserm.fr

Received 5 November 2008; Revised 19 March 2009; Accepted 22 May 2009; Published online 23 July 2009.

Abstract

CD160 is a glycosylphosphatidylinositol-anchored multimer expressed at the cell surface of subsets of cytotoxic T-lymphocytes and natural killer cells. Although CD160 is an important molecule for the control of cell-mediated cytotoxic responses, the mechanisms of regulation of its expression is unknown. We investigated the regulation of CD160 transcription by localizing and analyzing its promoter. The CD160 gene is encoded on chromosome 1, contains 6 exons with the translation initiation codon in exon 3. Bioinformatics analysis pointed to three potential promoter regions, two upstream of exon 1 and one in front of exon 3. RACE-PCR analysis identified a single transcription start site (TSS) and reporter gene transfections localized the active region immediately upstream of exon 1. Sequential deletion analysis led to the identification of a 371 bp sequence, located between -314 and +57 relative to the TSS, as the core promoter sequence driving CD160 gene transcription. Sequence alignment of the mouse and human CD160 genomic promoter region revealed a strong homology in the 371 bp sequence identified and pointed out to three conserved transcription factor binding sites for acute myelogenous leukemia-1 (AML-1), FREAC-4 and Sox17. Site-directed mutagenesis showed that the predicted AML-1 site is essential for the regulation of CD160 gene expression.