Identification of a novel cis-acting element for fibroblast-specific transcription of the FSP1 gene

Hirokazu Okada, Theodore M. Danoff, Andreas Fischer, Jesus M. Lopez-Guisa, Frank Strutz, Eric G. Neilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

The FSP1 gene encodes a filament-binding S100 protein with paired EF hands that is specifically expressed in fibroblasts. This led us to look for cis-acting elements in the FSP1 promoter that might engage nuclear transcription factors unique to fibroblasts. The first exon of FSP1 is noncoding, therefore, a series of luciferase reporter minigenes were created containing varying lengths of 5'-flanking sequence, the first intron, and the noncoding region of the second exon. A position and promoter-dependent proximal element between -187 and -88 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-l; TTGAT from -177 to -173 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 α1 and α2(I), and α1(III) collagens and the αSM-actin gene. We hypothesize that the selective engagement of FTS-1 elements may contribute to the mesenchymal phenotype of fibroblasts and perhaps other dedifferentiated cells.

Original languageEnglish (US)
Pages (from-to)F306-F314
JournalAmerican Journal of Physiology - Renal Physiology
Volume275
Issue number2 44-2
DOIs
StatePublished - Aug 1998

Keywords

  • Cis-acting element
  • FSP1
  • Fibroblast
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Urology

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