Temporal/spatial expression of nuclear receptor coactivators in the mouse lung.
Our laboratory has previously demonstrated that retinoic acid nuclear receptor, thyroid transcription factor-1 (TTF-1), and nuclear receptor coactivators such as cAMP response element binding protein (CREB) binding protein (CBP)/p300 and steroid receptor coactivator-1 (SRC-1) form an enhanceosome on the 5'-enhancer region of the human surfactant protein B gene. Immunohistochemistry was used to identify cells that coexpressed CBP/p300, SRC-1, retinoid X receptor, and TTF-1 in the developing and mature lung. CBP/p300 and SRC-1 were expressed in the adult mouse lung, CBP and p300 being present in both alveolar type I and type II epithelial cells and SRC-1 and TTF-1 being restricted to type II epithelial cells. CBP/p300, SRC-1, and TTF-1 were readily detected in the nuclei of developing respiratory epithelial tubules in fetal mice from embryonic days 10 to 18. CBP/p300 and SRC-1 were also detected in developing mesenchymal cells. These coactivators were coexpressed with TTF-1 and SP-B in human pulmonary adenocarcinoma cells (H441 cells) in vitro. Interaction assays with a two-hybrid reporter analysis demonstrated direct interactions among TTF-1, SRC-1, and CBP/p300 in H441 cells. These findings support a role for retinoic acid receptor and nuclear receptor coactivators in the regulation of SP-B gene expression in the respiratory epithelium.
Naltner
A
A
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Wert
S
S
Whitsett
J A
JA
Yan
C
C
D002282:Adenocarcinoma, Bronchiolo-Alveolar; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D004742:Enhancer Elements, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases; D006801:Humans; D008168:Lung / Q000737:chemistry / Q000254:growth & development / Q000502:physiology*; D008175:Lung Neoplasms; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D011510:Proteolipids / Q000235:genetics; D011663:Pulmonary Surfactants / Q000235:genetics; D020545:Respiratory Mucosa / Q000502:physiology; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020798:Two-Hybrid System Techniques
D017362:Cyclic AMP Response Element-Binding Protein; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1