A SAF binding site in the promoter region of human gamma-fibrinogen gene functions as an IL-6 response element.
Expression of fibrinogen is highly induced during inflammation, and such abnormal expression of this protein is considered as a major cardiovascular risk factor. IL-6 is one of the main mediators of abnormal expression of fibrinogen leading to the pathogenic conditions. Transient transfection and EMSA were performed to investigate the molecular mechanism of IL-6-induced gamma-fibrinogen gene expression in hepatic cells. Using progressively deleted 5' fragments of the gamma-fibrinogen promoter coupled to chloramphenicol acetyltransferase gene, an IL-6 responsive element located between positions -273 and -259 was identified. Mutation of this element abrogates IL-6 responsiveness of the gamma-fibrinogen promoter. Interaction of this promoter with a zinc finger transcription factor, serum amyloid A activating factor (SAF)-1, was demonstrated by EMSA. Furthermore, overexpression of wild-type SAF-1 in transfected liver cells can increase transcription of the gamma-fibrinogen promoter. These data show that transcription factor SAF-1 is involved in the regulation of IL-6-mediated induction of the human gamma-fibrinogen gene in liver cells.
Ray
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Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211, USA. Rayal@missouri.edu
D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D011401:Promoter Regions, Genetic / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D020218:Response Elements / Q000276:immunology*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D014157:Transcription Factors; C076035:c-MYC-associated zinc finger protein; D005340:Fibrinogen