STRUCTURAL CHARACTERISTICS OF THE 5' REGION OF THE HUMAN ICAM-1 GENE

The ICAM-1 glycoprotein, one of the major cellular adhesion molecules, exhibits a diverse and highly regulated tissue distribution. To better understand the regulatory mechanisms underlying its particular expression pattern, we have cloned the ICAM-1 gene from human leukocyte libraries. By hybridization with various DNA probes derived from different regions of the ICAM-1 cDNA, several clones were identified and isolated. Clone HWB 3R1, containing a 15kb DNA insert, was selected for further characterization. The HWB 3R1 clone hybridized with probes corresponding to the 3' as well as the 5' region of the ICAM-1 cDNA and gave rise to ICAM-1 expression after transfection into the ICAM-1 deficient MJP17 melanoma cell line. The identity of the expressed ICAM-1 was verified by reaction with five different monoclonal antibodies specific for ICAM-1. Sequence analysis of about 1.2kb of DNA around the ATG start codon revealed putative binding sites for various transcription factors situated in the 5' untranslated region as well as within the first intron. These include SP-1, AP-1 and NF-kB binding sites as well as interferon and retinoic acid responsive elements.