CLONING AND CHARACTERIZATION OF THE HUMAN INTERLEUKIN-3 (IL-3) IL-5 GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR BETA-C GENE -REGULATION BY ETS FAMILY MEMBERS

High-affinity receptors for interleukin-3 (IL-3), IL-5, and granulocyt e-macrophage colony-stimulating factor (GM-CSF) are composed of two di stinct subunits, a ligand-specific or chain and a common beta chain (b eta c) Whereas the mouse has two homologous beta subunits (beta c and beta IL-3), in humans, only a single beta chain is identified. We desc ribe here the isolation and characterization of the gene encoding the human IL-3/IL5/GM-CSF receptor beta subunit. The gene spans about 25 k b and is divided into 14 exons, a structure very similar to that of th e murine beta c/beta IL-3 genes. Surprisingly, we also found the remna nts of a second beta c chain gene directly downstream of beta c. We id entified a functional promoter that is active in the myeloid cell line s U937 and HL-60, but not in HeLa cells. The proximal promoter region, located from -103 to +33 bp, contains two GGAA consensus binding site s for members of the Ets family. Single mutation of those sites reduce s promoter activity by 70% to 90%. The 5' element specifically binds P U.1, whereas the 3' element binds a yet-unidentified protein. These fi ndings, together with the observation that cotransfection of PU.1 and other Ets family members enhances pc promoter activity in fibroblasts, reinforce the notion that GGAA elements play an important role in mye loid-specific gene regulation. (C) 7998 by The American Society of Hem atology.