Gene Structure and Expression of Human Thyroid Transcription Factor-1 in Respiratory Epithelial Cells

doi:10.1074/jbc.270.14.8108

Gene Structure and Expression of Human Thyroid Transcription Factor-1 in Respiratory Epithelial Cells (*)

From the Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039 and the
Division of Neonatology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2370

^§To whom correspondence should be addressed:
Children's Hospital Medical Center, Division of Pulmonary Biology, TCHRF, 3333 Burnet Ave., Cincinnati, OH 45229-3039.
Tel.: 513-559-4830; Fax: 513-559-7868.

Abstract

The human gene encoding thyroid transcription factor-1 (TTF-1), a homeodomain-containing nuclear transcription protein of the Nkx2 gene family, was isolated and characterized. Human TTF-1 was encoded by a single gene locus spanning approximately 3.3 kilobases and consisted of two exons and a single intron. The TTF-1 cDNA and polypeptide of 371 amino acids have been highly conserved, sharing 98% identity with the rat TTF-1 polypeptide. Human TTF-1 mRNA and polypeptide were selectively expressed in human and mouse pulmonary adenocarcinoma cell lines. In addition to its presence in thyroid gland epithelium, the human TTF-1 protein was detected by immunohistochemistry in human fetal lung as early as 11 weeks of gestation, being localized in the nuclei of epithelial cells of the developing airways. After birth, TTF-1 was selectively expressed in Type II epithelial cells in the alveoli and in subsets of bronchiolar epithelial cells in the conducting regions of the lung. The 5′-flanking region of the human TTF-1 gene directed transcription of luciferase cDNA in a lung epithelial cell-selective manner. The conservation and distribution of TTF-1 in the human respiratory tract support its role in the regulation of lung development and surfactant homeostasis.

Footnotes

↵* This work was supported by Center for Gene Therapy Grant HL51832, Center of Excellence in Molecular Biology Grant HL41496, the Cystic Fibrosis Foundation (RDP Center), and National Institutes of Health Grant HL14214 SCOR (to M. T. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) U19816[GenBank].
↵¹ The abbreviations used are:

TTF-1

thyroid transcription factor-1

SP

surfactant protein

CCSP

Clara cell secretory protein

kb

kilobase(s).
↵²P. H. G. Van Renterhen, G. Vassant, and D. Christophe, GenBank accession number X77910[GenBank].
↵³P. A. Bejarano, R. P. Baughman, P. W. Biddinger, M. A. Miller, C. Fenoglio-Preiser, and J. A. Whitsett, unpublished observations.
- Received December 14, 1994.
- Revision received January 19, 1995.