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

被引:35
作者
Okada, H [1 ]
Danoff, TM [1 ]
Fischer, A [1 ]
Lopez-Guisa, JM [1 ]
Strutz, F [1 ]
Neilson, EG [1 ]
机构
[1] Univ Penn, Penn Ctr Mol Studies Kidney Dis, Philadelphia, PA 19104 USA
关键词
FSP1; fibroblast; transcription; cis-acting element;
D O I
10.1152/ajprenal.1998.275.2.F306
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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-1; 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 alpha(1) and alpha(2)(I), and alpha(1)(III) collagens and the alpha SM-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.
引用
收藏
页码:F306 / F314
页数:9
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