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PMID: 8065304 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis.

Molecular and cellular biology ·Vol. 14 ·No. 9 ·1994-09-00 ·Pages 5671-81

Bohinski RJ, Di Lauro R, Whitsett JA

Abstract

We used the lung epithelial cell-specific surfactant protein B (SPB) gene promoter as a model with which to investigate mechanisms involved in transcriptional control of lung-specific genes. In a previous study, we showed that the SPB promoter specifically activated expression of a linked reporter gene in the continuous H441 lung cell line and that H441 nuclear proteins specifically protected a region of this promoter from bp -111 to -73. In this study, we further show that this region is a complex binding site for thyroid transcription factor 1 (TTF-1) and hepatocyte nuclear factor 3 (HNF-3). Whereas TTF-1 bound two highly degenerate and closely spaced sites, HNF-3 proteins bound a TGT3 motif (TGTTTGT) that is also found in several liver-specific gene regulatory regions, where it appears to be a weak affinity site for HNF-3. Point mutations of these binding sites eliminated factor binding and resulted in significant decreases in transfected SPB promoter activity. In addition, we developed a cotransfection assay and showed that a family of lung-specific gene promoters that included the SPB, SPC, SPA, and Clara cell secretory protein (CCSP) gene promoters were specifically activated by cotransfected TTF-1. We conclude that TTF-1 and HNF-3 are major activators of lung-specific genes and propose that these factors are involved in a general mechanism of lung-specific gene transcription. Importantly, these data also show that common factors are involved in organ-specific gene expression along the mammalian foregut axis.

MeSH Terms
Animals Base Sequence Binding Sites DNA-Binding Proteins/physiology Gene Expression Regulation Hepatocyte Nuclear Factor 3-alpha Hepatocyte Nuclear Factor 3-beta In Vitro Techniques Liver/physiology Lung/physiology Mice Molecular Sequence Data Nuclear Proteins/physiology Promoter Regions, Genetic Proteolipids/genetics Pulmonary Surfactants/genetics RNA, Messenger/genetics Thyroid Gland/physiology Thyroid Nuclear Factor 1 Transcription Factors/genetics,physiology Transcriptional Activation
Chemicals
DNA-Binding Proteins Foxa1 protein, mouse Foxa2 protein, mouse Hepatocyte Nuclear Factor 3-alpha Nkx2-1 protein, mouse Nuclear Proteins Proteolipids Pulmonary Surfactants RNA, Messenger Thyroid Nuclear Factor 1 Transcription Factors Hepatocyte Nuclear Factor 3-beta
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bohinski R J
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-2899.
Di Lauro R
Whitsett J A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.9.5671-5681.1994
Published
1994-09-00
Pages
5671-81
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359092
Subset
IM
Grants
NHLBI NIH HHS · HL-07527 · United States
NHLBI NIH HHS · HL-38859 · United States
External Links
PubMed source DOI: 10.1128/mcb.14.9.5671-5681.1994 PMC Full Text View journal details
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