Characterization of the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) gene promoter: nuclear factors that interact with an element shared by three lymphokine genes--those for GM-CSF, interleukin-4 (IL-4), and IL-5.
The region extending from -40 to -54 of the 5'-flanking region of the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) gene shows homology to sequences found in the 5'-flanking regions of other cytokine genes, those encoding interleukin-4 (IL-4), IL-5, and granulocyte colony-stimulating factor (G-CSF). This sequence element is referred to as conserved lymphokine element 0 (CLE0). Saturation mutagenesis of the CLE0 element indicates that in addition to the previously mapped region between -73 and -91 (CLE2+ GC box), the CLE0 element is necessary for induction of the mouse GM-CSF gene by phorbol myristate acetate/Ca ionophore (A23187) stimulation in T cells. The presence of the CLE0 element is necessary to observe stimulation of the transcription activity of the mouse GM-CSF promoter in vitro. Mobility shift assays revealed that this region forms an inducible DNA-protein complex, NF-CLE0, which consists of two complexes of similar mobility, NF-CLE0a and NF-CLE0b. NF-CLE0a and NF-CLE0b recognize the 3' half and 5' half of the CLE0 element, respectively, with an overlapping region recognized by both proteins. The recognition sequence of NF-CLE0a corresponds to the region required for induction by phorbol myristate acetate/A23187, while the recognition sequence of NF-CLE0b contains bases that have inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Miyatake
S
S
Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304-1104.
Shlomai
J
J
Arai
K
K
Arai
N
N
D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D000001:Calcimycin / Q000494:pharmacology; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D015848:Interleukin-5 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015848:Interleukin-5; D015847:Interleukin-4; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D004247:DNA; D013755:Tetradecanoylphorbol Acetate