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

J Biol Chem. 1995 Oct 20;270(42):24852-7. doi: 10.1074/jbc.270.42.24852.


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 bhe 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 than regulate lung epithelial cell-specific transcription of the human SP-B gene.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA / metabolism
  • Enhancer Elements, Genetic*
  • Homeodomain Proteins / physiology*
  • Humans
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic
  • Proteolipids / genetics*
  • Pulmonary Surfactants / genetics*
  • Simian virus 40 / genetics
  • Thymidine Kinase / genetics
  • Thyroid Nuclear Factor 1
  • Transcription Factors / physiology*


  • Homeodomain Proteins
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Proteolipids
  • Pulmonary Surfactants
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • DNA
  • Thymidine Kinase