Characterization of the gene for the human high affinity IgE receptor (Fc epsilon RI) alpha-chain.
The Fc epsilon RI couples the mast cell-surface binding of IgE and Ag to a complex series of intracellular events culminating in cell activation and degranulation. The alpha-chain of Fc epsilon RI constitutes the Ig-binding subunit of this heterotetrameric receptor, and is itself a member of the Ig gene superfamily. We have isolated a human genomic DNA clone containing the entire Fc epsilon RI alpha gene, and completely sequenced a region from 1257 bp 5' of the transcription start site, to 513 bp 3' of the last exon of the gene. As with the previously characterized rat and mouse genes, human Fc epsilon RI alpha consists of five exons and four introns, and spans 5889 bp of genomic DNA. The splice donor and acceptor sites deduced by comparison with the cDNA sequence corresponded exactly to the locations found in analogous rodent genes. By mapping the 5' end of Fc epsilon RI alpha 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 transcripts were seen, with a maximum of 60 nt of 5'-untranslated sequence. About 650 bp of DNA upstream of the ATG translation initiation codon were compared among human, rat, and mouse Fc epsilon RI alpha sequences in search of common motifs that might mediate conserved regulatory interactions with DNA binding proteins. A 172-bp region of the human Fc epsilon RI alpha 5'-flanking sequence was highly conserved in both rodent species. Further studies will be required to determine whether these or other sequences are involved in Fc epsilon RI alpha gene regulation.
Pang
J
J
R. W. Johnson Pharmaceutical Research Institute, Don Mills, Ontario, Canada.
Taylor
G R
GR
Munroe
D G
DG
Ishaque
A
A
Fung-Leung
W P
WP
Lau
C Y
CY
Liu
F T
FT
Zhou
L
L
D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000235:genetics*; D015183:Restriction Mapping; D016385:TATA Box; D014158:Transcription, Genetic
D018076:DNA, Complementary; D017455:Receptors, IgE