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J. Biol. Chem., Vol. 276, Issue 11, 7937-7942, March 16, 2001
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From the Department of Medicine (Hematology/Oncology), Walther
Oncology Center, Indiana University School of Medicine, Indianapolis,
Indiana 46202
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, H. B., Zhu, Y. X., Yin, T., Sledge, G., and Yang, Y. C. (1998) Proc. Natl.
Acad. Sci. U. S. A. 95, 13555-13560). 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 the Ets-1 site at 97 to 94 and the 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 the 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.
To whom correspondence should be addressed: Dept. of Pharmacology,
Case Western Reserve University School of Medicine, 2109 Adelbert Rd.,
W353 Cleveland, OH 44106-4965. Tel.: 216-368-6931; Fax: 216-368-3395;
E-mail: yxy36@po.cwru.edu.
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