Upstream enhancer activity in the human surfactant protein B gene is mediated by thyroid transcription factor 1

C. Yan, Z. Sever, J. A. Whitsett

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Abstract

Surfactant protein B (SP-B) is selectively expressed in bronchiolar and alveolar epithelial cells of the lung. We identified an upstream enhancer located in the 5'-flanking region of the human SP-B gene (-439 to -331 base pair, hSP-B(-439/-331)) by deletion analysis of SP-B-luciferase constructs assessed in transfection assays in vitro. The element cis-activated the expression of an SV40 promoter-luciferase reporter gene in a human pulmonary adenocarcinoma cell line (H441-4). Three distinct binding sites for the nuclear transcription protein, thyroid transcription factor 1 (TTF-1), were identified, and the purified TTF-1 homeodomain was bound to the region of hSP-B(-439/-331). Co-transfection of H441-4 cells with the expression vector pCMV-TTF-1 trans-activated the native human SP-B promoter and the SV40 promoter fused with the SP-B enhancer. Mutations of the TTF-1 binding sites in the upstream enhancer blocked TTF-1 binding and transactivation activity. In summary, TTF-1 interacts with distinct proximal (-80 to -110) and distal (-439 to -331) cis-acting elements that regulate lung epithelial cell- specific transcription of the human SP-B gene.

Original languageEnglish (US)
Pages (from-to)24852-24857
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number42
DOIs
StatePublished - Jan 1 1995

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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