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Papers In Press, published online ahead of print December 12, 2000
J. Biol. Chem, 10.1074/jbc.M007470200
Submitted on August 16, 2000
Revised on December 12, 2000
Accepted on December 12, 2000
Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4965
Corresponding Author: yxy36{at}po.cwru.edu
MRG1 [melanocyte-specific gene 1 (MSG1) related gene], a ubiquitously expressed transcription factor that interacts with p300/CBP, TATA-binding protein and Lhx2, is the founding member of a new family of transcription factors. Initial characterization of this newly discovered transcription factor has underscored its potential involvement in many important cellular processes through transcriptional modulation. We previously demonstrated that MRG1 can be induced by various biological stimuli (Sun et al. Proc. Natl. Acad. Sci. USA 95:13555-60, 1998). As a first step in understanding its role in different biological processes, we investigated mechanisms that regulate transcription of the mouse MRG1 gene in fibroblasts. Transient transfection of Rat1 fibroblast cells with sequential 5?-deletions of mouse MRG1 promoter-luciferase fusion constructs indicated that the ?104 to +121 region contains the full promoter activity. Deletion and site-directed mutations within this region revealed that Ets-1 site at ?97 to ?94 and Sp1 site at ?51 to ?46 are critical for MRG1 expression in fibroblasts. Gel mobility shift and supershift assays performed with Rat1 nuclear extracts identified nucleoprotein complexes binding to the Ets-1 site and the Sp1 site. In Drosophila SL2 cells which lack Sp and Ets family of transcription factors, expression of Sp1, Sp3, and Ets-1 or Elf-1 functionally stimulated MRG1 promoter activity in a synergistic manner. These results suggest that multiple transcription factors acting in synergy are responsible for MRG1 expression and the responsiveness of cells to different biological stimuli.
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