Identification of a novel cis-acting element for fibroblast
-specific transcription of the fsp1 gene.
Okada, Hirokazu, Theodore M. Danoff, Andreas Fischer, Jesus M. Lopez
-Guisa, Frank Strutz, and Eric G. Neilson.
Penn Center for the Molecular Studies of Kidney Diseases,
University of Pennsylvania, Philadelphia, PA
APStracts 5:0091F, 1998.
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 non-coding, therefore, a series of luciferase reporter
minigenes were created containing varying lengths of 5' flanking
sequence, the first intron, and the non-coding region of the second
exon. A position and promoter-dependent proximal element between -187
to -88 bps was shown to be active in fibthis 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 a1 and [alpha]2(I), and
[alpha]1(III) collagens and the aSM-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.
Received 21 July 1997; accepted in final form 30 April 1998.
APS Manuscript Number F237-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 8 May 1998