Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1.

Published

Journal Article

CCSP is a 16 kDa protein expressed selectively in the Clara cells of the lung. Cis-acting elements conferring Clara cell-specific expression of rat CCSP gene were contained within the sequences -320 to +57 of the rCCSP promoter. DNA-TTF-1 protein interactions were identified within the sequences -302 to -278 and -90 to -66 from the transcriptional start site of the rat CCSP gene promoter. In electrophoretic mobility shift assays, recombinant TTF-1 homeodomain protein bound to each site. Nuclear extracts from H441 adenocarcinoma cells bound to the TTF-1 binding sites, were supershifted by anti-TTF-1 antibody, and were competed by other TTF-1 DNA binding motifs. Mutations that replaced two nucleotides in each of the TTF-1 binding motifs disrupted TTF-1 binding to the rCCSP promoter. In HeLa cells, mutagenesis of both TTF-1 sites reduced transactivation by TTF-1, while the activities of single-site mutants were similar to that of the wild-type plasmid. In H441 cells, transactivation by TTF-1 was inhibited by mutations of each or both of the TTF-1 binding sites. TTF-1 activates transcription of the rCCSP gene, binding to distinct but interacting cis-acting elements in the 5'-flanking region of the gene.

Full Text

Duke Authors

Cited Authors

  • Zhang, L; Whitsett, JA; Stripp, BR

Published Date

  • February 28, 1997

Published In

Volume / Issue

  • 1350 / 3

Start / End Page

  • 359 - 367

PubMed ID

  • 9061032

Pubmed Central ID

  • 9061032

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/s0167-4781(96)00180-7

Language

  • eng

Conference Location

  • Netherlands