Published ahead of print on September 10, 2004, doi:10.1165/rcmb.2003-0422OC Am. J. Respir. Cell Mol. Biol., Volume 32, Number 1, January 2005, 35-43 A more recent version of this article appeared on January 1, 2005
Submitted on November 24, 2003 PLAGL2, a Zinc Finger Protein, Transactivates the Surfactant Protein-C PromoterMeng-Chun W Yang1,1 Department of Internal Medicine/Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, Texas, USA, 2 Dallas Veterans Affairs Medical Center, Dallas, Texas, USA * To whom correspondence should be addressed. E-mail: yih-sheng.yang{at}utsouthwestern.edu.
Expression of surfactant protein-C (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-1 (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 PLAGL2 (Pleiomorphic Adenoma Gene Like-2), a ubiquitously expressed zinc finger protein, as a trans-factor 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 according to 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 aTTF-1 independent manner. Both human and mouse SP-C promoters, but not the SP-B promoter, could be activated by PLAGL2 in transfected 293 as well as MLE12 cells. The expression of PLAGL2 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.
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