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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Functional Analysis of Human MUC7 Mucin Gene 5'-Flanking Region in Lung Epithelial Cells.

The human MUC7 gene encodes a low-molecular-mass mucin glycoprotein that functions in modulation of microbial flora in the oral cavity and respiratory tracts. MUC7 gene expression is tissue- and cell-specific, with dominant expression in salivary gland acinar cells. To begin to understand the molecular mechanisms responsible for controlling MUC7 gene expression, we analyzed the promoter activity of MUC7 5'-flanking region in a human lung epithelial cell line A549. We demonstrated that MUC7 gene is expressed constitutively in this cell line and is upregulated by TNF-alpha stimulation. The promoter activities of a 2,762-bp fragment of the human genomic DNA (-2,732/+30 bp) and its deletion series, subcloned into a luciferase reporter vector, were characterized at the basal level and under stimulation by TNF-alpha. The results indicated that the minimal functional MUC7 promoter is in the region of -138/+30 bp. This region also revealed the greatest increase in the promoter activity upon TNF-alpha stimulation. Two putative AP1-binding elements and one NF-kappaB-binding element were identified within the proximal promoter. Further analyses demonstrated that mutations of these elements dramatically reduced specific DNA-protein binding ability and reporter gene expression. AP1 elements played an essential role in the constitutive expression, while the NF-kappaB element was crucially important in the response to TNF-alpha stimulation, demonstrating that TNF-alpha activates MUC7 transcription via NF-kappaB signaling pathway.[1]


  1. Functional Analysis of Human MUC7 Mucin Gene 5'-Flanking Region in Lung Epithelial Cells. Li, S., Bobek, L.A. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
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