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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2000-2-18
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pubmed:abstractText |
Surfactant protein A (SP-A) is a member of the collectin family of innate host defense molecules expressed primarily in respiratory epithelial cells of the lung. SP-A concentrations are influenced by both cell-specific and ubiquitous nuclear proteins that regulate SP-A gene transcription in a cell-selective and temporally regulated manner. In this work, a consensus GATA-binding site (GBS) was identified at positions -69 to -64 of the mouse SP-A gene. The transcriptional activity of wild-type SP-A reporter constructs in HeLa cells was increased 5-10-fold when cotransfected with a GATA-6 expression plasmid. Deletion of the GBS completely blocked transactivation by GATA-6. Transfection of a construct expressing GATA-6-engrailed fusion protein inhibited basal expression of the SP-A/chloramphenicol acetyltransferase construct in MLE-15 cells. Nuclear extract proteins from MLE-15 cells bound to the GBS in the mouse SP-A gene, and a supershifted band was detected with a GATA-6-specific antibody. Transactivation of the wild-type SP-A constructs by GATA-6 increased transcriptional activity 7-10-fold, whereas thyroid transcription factor-1 (TTF-1) increased the activity of these constructs 12-18-fold. The effects of cotransactivating with both GATA-6 and TTF-1 expression constructs were additive. However, mutation of the TTF-1-binding sites alone or in combination decreased GATA-6 transactivation. Likewise, mutation of the GBS blocked TTF-1 activation of the SP-A promoter. In situ hybridization demonstrated GATA-6 mRNA in the peripheral epithelial cells of fetal mouse lung, consistent with the sites of SP-A expression. GATA-6 is expressed in respiratory epithelial cells and binds to a cis-acting element in the SP-A gene promoter, activating the transcriptional activity of the gene.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chloramphenicol O-Acetyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gata6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteolipids,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactant-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Pulmonary Surfactants,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/thyroid nuclear factor 1
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
14
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1043-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10625644-Animals,
pubmed-meshheading:10625644-Base Sequence,
pubmed-meshheading:10625644-Cell Line,
pubmed-meshheading:10625644-Cell Nucleus,
pubmed-meshheading:10625644-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:10625644-Conserved Sequence,
pubmed-meshheading:10625644-DNA-Binding Proteins,
pubmed-meshheading:10625644-GATA6 Transcription Factor,
pubmed-meshheading:10625644-Gene Expression Regulation,
pubmed-meshheading:10625644-Glycoproteins,
pubmed-meshheading:10625644-HeLa Cells,
pubmed-meshheading:10625644-Humans,
pubmed-meshheading:10625644-Lung,
pubmed-meshheading:10625644-Mice,
pubmed-meshheading:10625644-Molecular Sequence Data,
pubmed-meshheading:10625644-Mutagenesis, Site-Directed,
pubmed-meshheading:10625644-Nuclear Proteins,
pubmed-meshheading:10625644-Proteolipids,
pubmed-meshheading:10625644-Pulmonary Surfactant-Associated Protein A,
pubmed-meshheading:10625644-Pulmonary Surfactant-Associated Proteins,
pubmed-meshheading:10625644-Pulmonary Surfactants,
pubmed-meshheading:10625644-Rats,
pubmed-meshheading:10625644-Recombinant Fusion Proteins,
pubmed-meshheading:10625644-Recombinant Proteins,
pubmed-meshheading:10625644-Respiratory Mucosa,
pubmed-meshheading:10625644-Sequence Alignment,
pubmed-meshheading:10625644-Sequence Homology, Nucleic Acid,
pubmed-meshheading:10625644-Transcription, Genetic,
pubmed-meshheading:10625644-Transcription Factors,
pubmed-meshheading:10625644-Transcriptional Activation,
pubmed-meshheading:10625644-Transfection,
pubmed-meshheading:10625644-Zinc Fingers
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pubmed:year |
2000
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pubmed:articleTitle |
GATA-6 activates transcription of surfactant protein A.
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pubmed:affiliation |
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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