A TRANSCRIPTION ACTIVATOR WITH RESTRICTED TISSUE DISTRIBUTION REGULATES CELL-SPECIFIC EXPRESSION OF ALPHA-1(XI) COLLAGEN

Different regulatory programs are likely to control expression of the alpha 1(XI) collagen (COL11A1) gene in cartilaginous and non-cartilagi nous tissues and in coordination with different collagen genes Here, w e report the identification of a cis-acting element that is required f or constitutive and tissue-specific activity of the proximal COL11A1 p romoter, The element binds an apparently novel activator whose express ion is restricted mostly, but not exclusively, to cells of mesenchymal origin, Transient transfection experiments using wild-type and mutant constructs demonstrated the critical contribution of a 45-base pair u pstream element (FP9) to promoter activity, The same functional tests and DNA binding assays narrowed down the critical portion of FP9 to a 20-base pair sequence, which consists of an imperfect palindrome with strong homology to the GATA consensus motif. Despite being able to bin d GATA proteins in vitro, FP9 is actually recognized by a distinct sim ilar to 100-kDa polypeptide (FP9C) probably belonging to the zinc-fing er family of transcription factors. FP9C binding was mostly identified in nuclei from cells of mesenchymal origin, including those actively engaged in COL11A1 transcription, A positive correlation was also esta blished between the level of FP9C binding and the degree of cell diffe rentiation in vitro, Thus, FP9C represents an unusual example of tissu e-specific and differentiation-related transcription factor with overl apping expression in hard and soft connective tissues.