Pleiomorphic adenoma gene-like-2, a zinc finger protein, transactivates the surfactant protein-C promoter

Meng Chun W Yang, Jonathan C. Weissler, Lance S. Terada, Feitao Deng, Yih Sheng Yang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Expression of surfactant protein (SP)-C occurs principally in type II pneumocytes located in the distal lung alveolae. SP-C expression is thought to be primarily regulated by thyroid transcription factor (TTF)-1 and its associated proteins interacting with a previously defined promoter region between -197 and -158 in mice. We screened a human lung cDNA library using a modified yeast one-hybrid system and identified pleiomorphic adenoma gene-like (PLAGL)-2, a ubiquitously expressed zinc finger protein, as a transfactor of the SP-C promoter. The PLAGL2 DNA-binding site was located in the SP-C promoter proximal region close to the TTF-1 sites. This site was demonstrated to be functional by use of electrophoresis mobility shift assay, mutagenesis analysis, and transfection studies. PLAGL2 bound to DNA via its N-terminus zinc fingers and activated the SP-C promoter in a TTF-1-independent manner. Both human and mouse SP-C promoters, but not the SP-B promoter, could be activated by PLAGL2 in transfected human embryonic kidney-293 (HEK293) cells as well as in murine type II (MLE12) cells. The expression of PLACL2 in isolated human embryonic lung type II cells and its transactivation activity on the SP-C promoter suggest that PLAGL2 may modulate SP-C expression during lung development.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2005

Keywords

  • Gene expression
  • PLAGL2
  • SP-C
  • TTF-1
  • Zinc finger protein

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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