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Transcription factor GATA-5 selectively up-regulates mucin gene expression
Chun-Yan Ren1, Yoshimitsu Akiyama, Satoshi Miyake
1Department of Molecular Oncology, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Purpose:
Overlapping expression patterns of epithelial mucins, MUC1-MUC6, and transcription factor GATA-5 were reported previously. However, the functional relationship between them is poorly understood. The aim of the current study is to elucidate whether or not expression of mucin genes is regulated by GATA-5.
Methods:
GATA-5 was transiently overexpressed in COS-7 and 293T cells by plasmid transfection and/or adenovirus infection. GATA-5 expression was confirmed by Western blot analysis. Expression of mucin genes was studied by reverse-transcription-PCR. Reporter gene assays were employed to analyze the effect of GATA-5 on the promoter activity of mucin genes.
Results:
mRNA levels of MUC2, MUC3, and MUC4 were increased, whereas those of MUC1, MUC5AC, MUC5B, and MUC6 remained unchanged upon the overexpression of GATA-5 in both COS-7 and 293T cells. By means of luciferase assay, GATA-5 was found to activate the promoters of the human MUC2 and MUC4 genes. GATA-5 lacking the zinc finger domain impaired these functions.
Conclusions:
These findings indicate that GATA-5 may play important roles in the regulation of mucin expression and gastrointestinal epithelial cell differentiation.