Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent

Angela Naltner, Manely Ghaffari, Jeffrey A. Whitsett, Cong Yan

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Surfactant B (SP-B) is a 79-amino acid peptide critical to postnatal respiratory adaptation. Expression of SP-B by respiratory epithelial cells is regulated by developmental and hormonal influences at the level of gene transcription. Previous studies supported the role of retinoic acids (RA) and their receptors (RARs) in SP-B gene transcription. In the present study, RARα was detected in mouse alveolar type II epithelial cells where SP-B is synthesized and processed. Deletion and site-specific mutagenesis analysis identified clustered retinoic acid-responsive element sites in the 5'- flanking enhancer region of the hSP-B gene that bound RARα proteins. RAR coactivators ACTR, SRC-1, and transcriptional intermediary factor 2 (TIF2) stimulated human (h) SP-B promoter activity in a dose-dependent fashion in pulmonary adenocarcinoma H441 cells. In addition, an RAR-associated protein, CREB-binding protein (CBP), potentiated the effects of RAR on hSP-B promoter activity in H441 cells. Importantly, RA stimulation of the hSP-B promoter depends on tissue-specific thyroid transcription factor (TTF-1) DNA-binding sites. TTF-1 protein synergistically stimulated the hSP-B promoter with RARα, CBP, and nuclear receptor coactivators in H441 cells. In addition, TTF-1 interacted directly with RARα and TIF2 in the mammalian two-hybrid system. These findings support a model in which RAR/retinoid X receptor, TTF- 1, coactivators, and CBP form a transcription activation complex in the upstream enhancer region of the hSP-B gene.

Original languageEnglish (US)
Pages (from-to)56-62
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number1
DOIs
StatePublished - Jan 7 2000
Externally publishedYes

Fingerprint

CREB-Binding Protein
Tretinoin
Surface-Active Agents
Transcription
Genes
Nuclear Receptor Coactivators
Retinoid X Receptors
Alveolar Epithelial Cells
Mutagenesis
Retinoic Acid Receptors
Proteins
5' Flanking Region
Site-Directed Mutagenesis
Hybrid systems
Transcriptional Activation
Transcription Factors
Epithelial Cells
Chemical activation
Binding Sites
Tissue

ASJC Scopus subject areas

  • Biochemistry

Cite this

Retinoic acid stimulation of the human surfactant protein B promoter is thyroid transcription factor 1 site-dependent. / Naltner, Angela; Ghaffari, Manely; Whitsett, Jeffrey A.; Yan, Cong.

In: Journal of Biological Chemistry, Vol. 275, No. 1, 07.01.2000, p. 56-62.

Research output: Contribution to journalArticle

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