Cloning and characterization of the human interleukin-3 (IL-3)/IL-5/ granulocyte-macrophage colony-stimulating factor receptor betac 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 chain and a common beta chain (betac). Whereas the mouse has two homologous beta subunits (betac and betaIL-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/IL-5/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 betac/betaIL-3 genes. Surprisingly, we also found the remnants of a second betac chain gene directly downstream of betac. 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 betac promoter activity in fibroblasts, reinforce the notion that GGAA elements play an important role in myeloid-specific gene regulation.
van Dijk
T B
TB
Department of Pulmonary Diseases, University Hospital Utrecht, Utrecht, The Netherlands.
Baltus
B
B
Caldenhoven
E
E
Handa
H
H
Raaijmakers
J A
JA
Lammers
J W
JW
Koenderman
L
L
de Groot
R P
RP
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D053648:Cytokine Receptor Common beta Subunit; D019281:Dimerization; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D005796:Genes; D018922:HL-60 Cells / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D055503:Protein Multimerization; D011544:Pseudogenes; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D016185:Receptors, Interleukin-3 / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D020298:U937 Cells / Q000378:metabolism
C115876:CSF2RB protein, human; D053648:Cytokine Receptor Common beta Subunit; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D016185:Receptors, Interleukin-3