Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene.
The gene for human granulocyte/macrophage colony-stimulating factor (GM-CSF) is expressed in a tissue-specific as well as an activation-dependent manner. The interaction of nuclear proteins with the promoter region of the GM-CSF gene that is likely to be responsible for this pattern of GM-CSF expression was investigated. We show that nuclear proteins interact with DNA fragments from the GM-CSF promoter in a cell-specific manner. A region spanning two cytokine-specific sequences, cytokine 1 (CK-1, 5' GAGATTCCAC 3') and cytokine 2 (CK-2, 5' TCAGGTA 3') bound two nuclear proteins [nuclear factor (NF)-GMa and NF-GMb] from GM-CSF-expressing cells in gel retardation assays. NF-GMb was inducible with phorbol 12-myristate 13-acetate and accompanied induction of GM-CSF message. NF-GMb was absent in cell lines not producing GM-CSF, some of which had other distinct binding proteins. NF-GMa and NF-GMb eluted from a heparin-Sepharose column at 0.3 and 0.6 M KCl, respectively. We hypothesize that the sequences CK-1 and CK-2 bind specific proteins and regulate GM-CSF transcription.
Shannon
M F
MF
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Gamble
J R
JR
Vadas
M A
MA
D001483:Base Sequence; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006098:Granulocytes; D006801:Humans; D008264:Macrophages; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012689:Sequence Homology, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D004268:DNA-Binding Proteins; D004247:DNA; D013755:Tetradecanoylphorbol Acetate