A mechanism of transcriptional regulation of the CSF-1 gene by interferon-gamma.
Interferon (IFN)-gamma exerts multiple functions including antiviral, anti-proliferative and immunomodulatory activities, which are mediated through the JAK-STAT pathway. We observed that IFN-gamma significantly increases the production of colony stimulating factor-1 (CSF-1) by a human lung carcinoma cell line, A549. To gain insight into this mechanism, we determined the unknown nucleotide sequences of 5'-flanking region of human CSF-1 gene. About 60 bases upstream of the transcription start site of the CSF-1 gene contains a possible gamma interferon activated site (GAS), TTCCCATAA. The promoter assay and the electrophoretic mobility gel shift assay revealed that IFN-gamma stimulates transcription of the CSF-1 gene through this sequence, which binds STAT1.
Tsuchimoto
Daisuke
D
Division of Molecular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. daisuke@bioreg.kyushu-u.ac.jp
Tojo
Arinobu
A
Asano
Shigetaka
S
D001483:Base Sequence; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D016173:Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D050832:Interferon-Stimulated Gene Factor 3; C079868:gamma interferon activation factor; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma