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 |
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Authors: | van Dijk Thamar B; Baltus Belinda; Caldenhoven Eric; Handa Hiroshi; Raaijmakers Jan AM; Lammers Jan-Willem J; Koenderman Leo; de Groot Rolf P |
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Institution: | From the Department of Pulmonary Diseases, University HospitalUtrecht, Utrecht, The Netherlands; and the Faculty of Bioscience andBiotechnology, Tokyo Institute of Technology, Midoriku, Yokohama,Japan. |
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Abstract: | High-affinity receptors for interleukin-3 (IL-3), IL-5, andgranulocyte-macrophage colony-stimulating factor (GM-CSF) are composedof two distinct subunits, a ligand-specific chain and a common chain ( c). Whereas the mouse has two homologous subunits ( cand IL-3), in humans, only a single chain is identified. Wedescribe here the isolation and characterization of the gene encodingthe human IL-3/IL-5/GM-CSF receptor subunit. The gene spans about25 kb and is divided into 14 exons, a structure very similar to that ofthe murine c/ IL-3 genes. Surprisingly, we also found the remnantsof a second c chain gene directly downstream of c. We identifieda functional promoter that is active in the myeloid cell lines U937 andHL-60, but not in HeLa cells. The proximal promoter region, locatedfrom 103 to +33 bp, contains two GGAA consensus binding sites formembers of the Ets family. Single mutation of those sites reducespromoter activity by 70% to 90%. The 5 element specificallybinds PU.1, whereas the 3 element binds a yet-unidentifiedprotein. These findings, together with the observation thatcotransfection of PU.1 and other Ets family members enhances cpromoter activity in fibroblasts, reinforce the notion that GGAAelements play an important role in myeloid-specific gene regulation. |
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