An unusual participation for lour RARE-like mollis in reiinoid-stimulalcd transcription of human thioredoxin gene

Reen Wu, V. Chang, S. P M Reddy

Research output: Contribution to journalArticle

Abstract

Thioredoxin (Trx) is a 12 kd protein knowingly involved in various redo reactions essential for cell growth and injury/repair. We have previously shown, based on nuclear run-on assay, lhat the regulation of Trx gene expression in human and non-human primate airway epithelium hy retinoid occurred at the transcriptional level. To further elucidate the transcnplional mechanism, the ,Vflanking region of human Trx gene was isolated, sequenced, and subcloncd to an expression vector with a reporter gene, chloramphenicol acelyltransferase (CAT). DNA sequence information revealed the presence of TATA box and four RARElike half sites at -28, -426. -453, -507. and -626 bp. respectively, in the 5'flanking region of human Trx gene. Using the deletion and site-directed mutation analyses, we have demonstrated the importance of the first (at -426 bp) and 2nd (at -453 bp) RARE-like motifs in the regulation of Trx gene expression hy retinoic acid. However, mutations or deletions of third and fourth RARE-like sites would decrease the trancriptional activation. These results were further supported by both the in vivo and in vitro footprinting data. In vitro gel mobility shift assay demonstrated the interactions between these sites with RAR-a and RAR-Y proteins. These results suggest an unusual participation of these four RARE-like motifs in the regulation of human Trx gene expression by retinoic acid.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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