An upstream negative regulatory element in human granulocyte-macrophage colony-stimulating factor promoter is recognised by AP1 family members

• Published in: FEBS letters Vol. 440; no. 1; pp. 119 - 124
• Main Authors: Gramigni, Claudia, Penco, Silvana, Bianchi-Scarrà, Giovanna, Ravazzolo, Roberto, Garrè, Cecilia
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 27.11.1998
• Subjects: Antibodies; AP1; Binding, Competitive; CAT, chloramphenicol acetyltransferase; Consensus Sequence; DNA Footprinting; EMSA, electrophoretic mobility shift assay; Gene Expression Regulation, Neoplastic; Genes, Reporter; GM-CSF, granulocyte-macrophage colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Humans; Negative cis element; Oligonucleotides; Point Mutation; Promoter Regions, Genetic - genetics; Proto-Oncogene Proteins c-fos - immunology; Proto-Oncogene Proteins c-fos - metabolism; Proto-Oncogene Proteins c-jun - immunology; Proto-Oncogene Proteins c-jun - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RT-PCR, reverse transcriptase polymerase chain reaction; Sequence Deletion; TPA, 12-O-tetradecanoyl phorbol-13-acetate; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - immunology; Transcription Factor AP-1 - metabolism; Transcriptional regulation; Transfection; TRE, TPA responsive element; Tumor Cells, Cultured; U87MG; AP1; Granulocyte-macrophage colony-stimulating factor; RT-PCR, reverse transcriptase polymerase chain reaction; U87MG; CAT, chloramphenicol acetyltransferase; Negative cis element; TPA, 12- O-tetradecanoyl phorbol-13-acetate; GM-CSF, granulocyte-macrophage colony-stimulating factor; Transcriptional regulation; EMSA, electrophoretic mobility shift assay; TRE, TPA responsive element
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01443-4

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine involved in haematopoiesis and host defence. Production of GM-CSF has been detected in tumour cells including the U87MG astrocytoma cell line. Previous studies have been focused on the regulatory role of the proximal region of the GM-CSF promoter. Our studies on the distal region of the promoter in U87MG cells identify a negative cis element (−1377/−1298) which contains a AP1-like site able to bind c- jun and c- fos transcription factors, according to the results of DNA/protein binding assays. Mutagenesis of the AP1-like site eliminates AP1 binding and the negative effect on promoter activity.