The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families.
We have shown that a large fragment (-2339 to +57) from the rat CC10 gene directed lung-specific expression of a reporter construct in transgenic animals. Upon transfection, a smaller fragment (-165 to +57) supported reporter gene expression exclusively in the Clara cell-like NCI-H441 cell line, suggesting that a Clara cell-specific transcriptional element resided on this fragment (B. R. Stripp, P. L. Sawaya, D. S. Luse, K. A. Wikenheiser, S. E. Wert, J. A. Huffman, D. L. Lattier, G. Singh, S. L. Katyal, and J. A. Whitsett, J. Biol. Chem. 267:14703-14712, 1992). The interactions of nuclear proteins with a particular segment of the CC10 promoter which extends from 79 to 128 bp upstream of the CC10 transcription initiation site (CC10 region I) have now been studied. This sequence can stimulate both in vitro transcription in H441 nuclear extract and transient expression of reporter constructs in H441 cells. Electrophoretic mobility shift assays using extracts from H441, HeLa, rat liver, and fetal sheep lung cells were used to demonstrate that members of the AP-1, octamer, and HNF-3 families bind to CC10 region I. Transcription factors from H441 cells which are capable of binding to CC10 region I are either absent in HeLa, rat liver, and fetal sheep lung extracts or enriched in H441 extracts relative to extracts from non-Clara cells.
Sawaya
P L
PL
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Ohio 45267-0524.
Stripp
B R
BR
Whitsett
J A
JA
Luse
D S
DS
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051541:Hepatocyte Nuclear Factor 3-alpha; D051863:Host Cell Factor C1; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D050811:Octamer Transcription Factor-1; D011506:Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014598:Uteroglobin
D004268:DNA-Binding Proteins; C496499:FOXA1 protein, human; C496501:Foxa1 protein, rat; C497692:HCFC1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D051863:Host Cell Factor C1; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; C494168:Pou2f1 protein, rat; D011506:Proteins; D016755:Proto-Oncogene Proteins c-jun; C556389:SCGB1A1 protein, human; C556391:Scgb1a1 protein, rat; D014157:Transcription Factors; D004247:DNA; D014598:Uteroglobin