Structure of the human APO‐1 gene

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Abstract
APO‐1/Fas (CD95) is a type 1 transmembrane protein that belongs to the tumor necrosis factor/nerve growth factor receptor family characterized by cysteine‐rich extracellular domains. Cross‐linking of APO‐1 mediates apoptosis in a variety of cells. In the present study we report the isolation and characterization of the human APO‐1 gene spanning approximately 25 kb of human chromosome 10. The gene consists of nine exons (25 bp to > 1.44 kb) separated by eight introns (152 bp to ∼ 12 kb). The boundaries of exon 2 to 5 encoding the extracellular region do not match the boundaries of the three APO‐1 protein subdomains. Exon structure and functional protein domains correspond for exon 6 encoding the transmembrane region and for exon 9 encoding the „death domain”︁. By a polymerase chain reaction‐based approach we localized major transcriptional start sites in human spleen cells 77 and 73 nucleotides upstream of the translation initiation codon of the human APO‐1 gene. Minor initiation sites were found at positions −128, −111, −91, and −74. The 5′ flanking sequence of the human APO‐1 gene is GC rich, contains a high number of CpG dinucleotides and lacks a consensus TATA box. Consensus binding sites for the transcription factors Sp1, AP‐1, AP‐2, GAF, NF‐χB, and NF‐AT were found. The elucidation of the human APO‐1 gene structure will facilitate the study of its involvement in various diseases such as in autoimmunity.