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J Biol Chem. 1995 Mar 24;270(12):6531-6.

Lung cell-specific expression of the murine surfactant protein A (SP-A) gene is mediated by interactions between the SP-A promoter and thyroid transcription factor-1.

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1
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039.

Erratum in

  • J Biol Chem 1995 Jul 7;270(27):16482.

Abstract

Cis-acting elements determining lung epithelial cell-selective transcription of the murine surfactant protein A (SP-A) gene were identified between nucleotide positions -255 and -57. This region of the murine SP-A gene contained nucleotide sequences consistent with thyroid transcription factor-1 (TTF-1) binding motifs. An SP-A-CAT plasmid containing the TTF-1 binding sites was transcriptionally active in mouse lung epithelial (MLE-15) cells but not in HeLa, 3T3, or H441 cells. However, transcription of the SP-A-CAT construct was activated after cotransfection of HeLa cells with a vector expressing recombinant TTF-1, pCMV-TTF-1. Recombinant TTF-1 homeodomain protein bound to four distinct binding sites located between nucleotides -166 to -117 [corrected]. Proteins in nuclear extracts of MLE-15 cells bound TTF-1 binding sites and were supershifted by TTF-1 antibody. Mutations of three of the TTF-1 binding sites in this region reduced expression of the SP-A-CAT construct in transfected MLE-15 cells and reduced transactivation in HeLa cells. TTF-1 interacts with complex protein/DNA binding sites located in the 5'-flanking region of the murine SP-A gene enhancing lung epithelial cell-specific expression in vitro.

PMID:
7896788
DOI:
10.1074/jbc.270.12.6531
[Indexed for MEDLINE]
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