CHARACTERIZATION OF THE GENE FOR THE HUMAN HIGH-AFFINITY IGE RECEPTOR(FC-EPSILON-RI) ALPHA-CHAIN

The FcepsilonRI couples the mast cell-surface binding of IgE and Ag to a complex series of intracellular events culminating in cell activati on and degranulation. The alpha-chain of FcepsilonRI constitutes the I g-binding subunit of this heterotetrameric receptor, and is itself a m ember of the Ig gene superfamily. We have isolated a human genomic DNA clone containing the entire FcepsilonRIalpha gene, and completely seq uenced a region from 1257 bp 5' of the transcription start site, to 51 3 bp 3' of the last exon of the gene. As with the previously character ized rat and mouse genes, human FcepsilonRIalpha consists of five exon s and four introns, and spans 5889 bp of genomic DNA. The splice donor and acceptor sites deduced by comparison with the cDNA sequence corre sponded exactly to the locations found in analogous rodent genes. By m apping the 5' end of FcepsilonRIalpha transcripts we found three major transcription initiation sites 24, 27, and 29 bp upstream of the ATG translation initiation codon. As well, several longer minor transcript s were seen, with a maximum of 60 nt of 5'-untranslated sequence. Abou t 650 bp of DNA upstream of the ATG translation initiation codon were compared among human, rat, and mouse FcepsilonRIalpha sequences in sea rch of common motifs that might mediate conserved regulatory interacti ons with DNA binding proteins. A 172-bp region of the human FcepsilonR Ialpha 5'-flanking sequence was highly conserved in both rodent specie s. Further studies will be required to determine whether these or othe r sequences are involved in FcepsilonRIalpha gene regulation.