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A position and promoter-dependent proximal element between \u2212187 and \u221288 bp was shown to be active in fibroblasts but not in epithelium. Sequence in the first intron from +777 to +964 had an enhancing effect that was not cell type specific. Hsv TK reporter constructs driven by this promoter\/intron cassette in transgenic mice were coexpressed appropriately with FSP1 in tissue fibroblasts. Gel mobility shift competitor assays identified a novel domain, FTS-1 (fibroblast transcription site-1; TTGAT from \u2212177 to \u2212173 bp), that specifically interacts with nuclear extracts from fibroblasts. The necessity of this binding site was confirmed by site-specific mutagenesis. Database searches also turned up putative FTS-1 sites in the early promoter regions of other fibroblast expressed proteins, including the \u03b1<jats:sub>1<\/jats:sub>and \u03b1<jats:sub>2<\/jats:sub>(I), and \u03b1<jats:sub>1<\/jats:sub>(III) collagens and the \u03b1SM-actin gene. 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