A transcription activator with restricted tissue distribution regulates cell-specific expression of α1(XI) collagen

Akihiro Kinoshita, Patricia Greenwel, Shizuko Tanaka, Maurizio Di Liberto, Hidekatus Yoshioka, Francesco Ramirez

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Diffrent regulatory programss are likely to control expression of the α1 (XI) collagen (COL11A1) gene in cartilaginous and non-cartilaginous tissues and in coordination with different collagen genes. Here, we report the identification of a cis-acting element that is required for constitutive and tissue-specific activity of the proximal COL11A1 promoter. The element binds an apparently novel activator whose expression is restricted mostly, but not exclusively, to cells of mesenchymal origin. Tramsient transfection experiments using wild-type amd mutant constructs demonstrated the critical contribution of a 45-base pair upstream 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 bind GATA proteins in vitro, FP9 is actually recognized by a distinct ~100-kDa polypeptide (FP9C) probably belonging to the zinc-finger family of transcription factors. FP9C binding was mostly identified in nuclei from cells of mesenchymal origin, including those actively engaged in CO11A1 transcription. A positive correlation was also established between the level of FP9C binding and the degree of cell differentiation in vitro. Thus, FP9C represents an unusual example of tissue-specific and diffrentiation-related transcription factor with overlapping expression in hard and soft connective tissues.

Original languageEnglish
Pages (from-to)31777-31784
Number of pages8
JournalJournal of Biological Chemistry
Volume272
Issue number50
DOIs
StatePublished - 12 Dec 1997

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