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

Abstract

AbstractHigh-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  chain and a common β chain (βc). Whereas the mouse has two homologous β subunits (βc and βIL-3), in humans, only a single β chain is identified. We describe here the isolation and characterization of the gene encoding the human IL-3/IL-5/GM-CSF receptor β subunit. The gene spans about 25 kb and is divided into 14 exons, a structure very similar to that of the murine βc/βIL-3 genes. Surprisingly, we also found the remnants of a second βc chain gene directly downstream of βc. 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 βc promoter activity in fibroblasts, reinforce the notion that GGAA elements play an important role in myeloid-specific gene regulation.