Cloning and characterization of the human interleukin-3 (IL-3) IL-5 granulocyte-macrophage colony-stimulating factor receptor βc gene:: Regulation by Ets family members

High-affinity receptors for interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are composed of two distinct subunits, a ligand-specific or chain and a common beta chain (beta 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 describe here the isolation and characterization of the gene encoding the human IL-3/IL5/GM-CSF receptor beta subunit. The gene spans about 25 kb and is divided into 14 exons, a structure very similar to that of the murine beta c/beta IL-3 genes. Surprisingly, we also found the remnants of a second beta c chain gene directly downstream of beta c. We identified a functional promoter that is active in the myeloid cell lines U937 and HL-60, but not in HeLa cells. The proximal promoter region, located from -103 to +33 bp, contains two GGAA consensus binding sites for members of the Ets family. Single mutation of those sites reduces promoter activity by 70% to 90%. The 5' element specifically binds PU.1, whereas the 3' element binds a yet-unidentified protein. These findings, 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 myeloid-specific gene regulation. (C) 7998 by The American Society of Hematology.