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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3636-3646
Cloning and Characterization of the Human Interleukin-3 (IL-3)/IL-5/
Granulocyte-Macrophage Colony-Stimulating Factor Receptor  c Gene:
Regulation by Ets Family Members
Thamar B. van Dijk,
Belinda Baltus,
Eric Caldenhoven,
Hiroshi Handa,
Jan A.M. Raaijmakers,
Jan-Willem J. Lammers,
Leo Koenderman, and
Rolf P. de Groot
From the Department of Pulmonary Diseases, University Hospital
Utrecht, Utrecht, The Netherlands; and the Faculty of Bioscience and
Biotechnology, Tokyo Institute of Technology, Midoriku, Yokohama,
Japan.
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  chain and a common  chain (c). Whereas the mouse has two homologous subunits (c
and IL-3), in humans, only a single chain is identified. We
describe here the isolation and characterization of the gene encoding
the human IL-3/IL-5/GM-CSF receptor subunit. The gene spans about
25 kb and is divided into 14 exons, a structure very similar to that of
the murine c/IL-3 genes. Surprisingly, we also found the remnants
of a second c chain gene directly downstream of 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 c
promoter activity in fibroblasts, reinforce the notion that GGAA
elements play an important role in myeloid-specific gene regulation.
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