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HSP47 is a collagen-binding heat shock protein and is assumed to act as a molecular chaperone in the biosynthesis and secretion of procollagen. As the synthesis of HSP47 is closely correlated with that of collagen in various cell lines and tissues, we performed a promoter/ reporter assay using HSP47-producing and nonproducing cells. 280 base pairs (bp(s)) of upstream promoter were shown to be necessary for the basal expression but not to be enough for the cell type-specific expression. When the first and the second introns were introduced downstream of this 280-bp region, marked up-regulation of the reporter activity was observed in HSP47-producing cells but not in nonproducing cells. This was confirmed in transgenic mice by staining the lacZ gene product under the control of the 280-bp upstream promoter and the introns. Staining was observed in skin, chondrocytes, precursor of bone, and other HSP47/collagen-producing tissues. A putative Sp1-binding site at ؊210 bp in the promoter, to which Sp3 and an unidentified protein bind, was shown to be responsible for this up-regulation when combined with the introns. However no difference in the binding to this probe was observed between HSP47-producing and nonproducing cells. The responsible region for cell type-specific upregulation was found to be located in a 500-bp segment in the first intron. On electrophoresis mobility shift assay using this 500-bp probe, specific DNA-protein complexes were only observed in HSP47-producing cell extracts. These results suggest that two separate elements are necessary for the cell type-specific expression of the hsp47 gene; one is a putative Sp1-binding site at ؊210 bp necessary for basal expression, and the other is a 500-bp region within the first intron, required for cell typespecific expression.Heat shock proteins (HSPs) 1 are a highly conserved set of proteins that can be induced by heat shock and other environmental stresses. Generally, most stress proteins are expressed not only under stress conditions but also under normal growth conditions and known to play important roles in protein folding and assembly. They are now generally known as molecular chaperones. The mechanism for heat induction of HSPs is well studied and now known to be transcriptionally regulated by the interaction of heat shock factors with heat shock elements (HSEs), which locate in the promoter region of HSPs (1).HSP47 was identified as a collagen-binding 47-kDa glycoprotein (pI ϭ 9.0) (2) and proved to be a heat shock protein (3-6). This protein belongs to the serine protease inhibitor (serpin) superfamily containing a serpin signature sequence (7). HSP47 resides in the endoplasmic reticulum (ER), as inferred from the presence of a carboxyl-terminal RDEL sequence similar to the ER retrieval signal, KDEL (8 -13). HSP47 binds to nascent procollagen chains in the ER of collagen-secreted cells and dissociates from them before reaching the cis-Golgi apparatus (4, 6, 14). Thus HSP47 functions as a collagen-specific molecular chaperone (15).The expression of HS...

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