THE MURINE INTERLEUKIN-3 RECEPTOR-ALPHA SUBUNIT GENE - CHROMOSOMAL LOCALIZATION, GENOMIC STRUCTURE, AND PROMOTER FUNCTION

The interleukin-3 receptor (IL-3R) is composed of alpha and beta subun its, members of the class I cytokine receptor family. Here we describe isolation and characterization of the chromosomal gene for the mouse IL-3R alpha subunit (mIL-3R alpha). Whereas the human IL-3R alpha gene is tightly linked with the granulocyte-macrophage colony-stimulating factor receptor alpha subunit (GM-CSFR alpha) gene in the pseudoautoso mal region of the X and Y chromosomes, the mIL-3R alpha gene (II3ra) i s located in the proximal region of mouse chromosome 14, separated fro m the mouse GM-CSFR alpha gene, which is on chromosome 19. The mIL-3R alpha gene spans about 10 kb and is divided into 12 exons. All the exo n-intron boundaries possess the splicing junction consensus sequences (5'GT-AG3'), and the whole genomic structure is similar to those of th e previously reported class I cytokine receptor genes. There are two m ajor transcription initiation sites that are located at 215 and 188 nu cleotides upstream of the initiator codon. The promoter region is GC-r ich and contains potential binding sites for GATA, Ets, c-myb,, Sp1, A p-2, and G-C boxes, but not a typical TATA or CAAT sequence. A fusion gene containing 0.8 kb of the 5' noncoding sequence linked to the fire fly luciferase gene directed the transcription in mouse mast cells but not in fibroblasts or T cells, suggesting that this promoter function s in a cell type-specific manner. Further sequential deletion of the 5 ' region suggests two potential regulatory regions for transcription o f the mIL-3R alpha gene. (C) 1995 by The American Society of Hematolog y.