TY - JOUR
T1 - The basic helix-loop-helix-zipper transcription factor USF1 regulates expression of the surfactant protein-A gene
AU - Gao, Erwei
AU - Wang, Ying
AU - Alcorn, Joseph L.
AU - Mendelson, Carole R.
PY - 1997
Y1 - 1997
N2 - Expression of the rabbit pulmonary surfactant protein A (SP-A) gene is lung-specific, occurs primarily in type II cells, and is developmentally regulated. We previously identified two E-box-like enhancers, termed the distal binding element (DBE) and proximal binding element (PBE), in the 5'- flanking region of the rabbit SP-A gene. In the present study, the PBE was used to screen a rabbit fetal lung cDNA expression library; a cDNA insert was isolated which is highly similar in sequence to human upstream stimulatory factor 1 (hUSF1). By use of reverse transcription polymerase chain reaction, two isoforms of rabbit USF1 (rUSF1) mRNAs were identified in fetal rabbit lung and other tissues. The levels of rUSF1 mRNAs reach a peak in fetal rabbit lung at 23 days gestation, in concert with the time of initiation of SP-A gene transcription. Binding complexes of nuclear proteins obtained from fetal rabbit lung tissue and isolated type II cells with the DBE and PBE were super-shifted by the addition of anti-rUSF1 IgG. Binding activity was enriched in type II cells compared with lung fibroblasts. Overexpression of rUSF1s in A549 adenocar-cinoma cells positively regulated SP-A promoter activity of cotransfected reporter gene constructs. It is suggested that rUSF1s, which bind to two E-box elements in the SP-A gene 5'-flanking region, may serve a key role in the regulation of SPA gene expression in pulmonary type II cells.
AB - Expression of the rabbit pulmonary surfactant protein A (SP-A) gene is lung-specific, occurs primarily in type II cells, and is developmentally regulated. We previously identified two E-box-like enhancers, termed the distal binding element (DBE) and proximal binding element (PBE), in the 5'- flanking region of the rabbit SP-A gene. In the present study, the PBE was used to screen a rabbit fetal lung cDNA expression library; a cDNA insert was isolated which is highly similar in sequence to human upstream stimulatory factor 1 (hUSF1). By use of reverse transcription polymerase chain reaction, two isoforms of rabbit USF1 (rUSF1) mRNAs were identified in fetal rabbit lung and other tissues. The levels of rUSF1 mRNAs reach a peak in fetal rabbit lung at 23 days gestation, in concert with the time of initiation of SP-A gene transcription. Binding complexes of nuclear proteins obtained from fetal rabbit lung tissue and isolated type II cells with the DBE and PBE were super-shifted by the addition of anti-rUSF1 IgG. Binding activity was enriched in type II cells compared with lung fibroblasts. Overexpression of rUSF1s in A549 adenocar-cinoma cells positively regulated SP-A promoter activity of cotransfected reporter gene constructs. It is suggested that rUSF1s, which bind to two E-box elements in the SP-A gene 5'-flanking region, may serve a key role in the regulation of SPA gene expression in pulmonary type II cells.
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U2 - 10.1074/jbc.272.37.23398
DO - 10.1074/jbc.272.37.23398
M3 - Article
C2 - 9287355
AN - SCOPUS:0030846296
SN - 0021-9258
VL - 272
SP - 23398
EP - 23406
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 37
ER -