THE LUNG-SPECIFIC CC10 GENE IS REGULATED BY TRANSCRIPTION FACTORS FROM THE AP-1, OCTAMER, AND HEPATOCYTE NUCLEAR FACTOR-III FAMILIES

We have shown that a large fragment (-2339 to +57) from the rat CC10 g ene directed lung-specific expression of a reporter construct in trans genic animals. Upon transfection, a smaller fragment (-165 to +57) sup ported 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. L use, K. A. Wikenheiser, S. E. Wert, J. A. Huffman, D. L. Lattier, G. S ingh, S. L. Katyal, and J. A. Whitsett, J. Biol. Chem. 267:14703-14712 , 1992). The interactions of nuclear proteins with a particular segmen t of the CC10 promoter which extends from 79 to 128 bp upstream of the CC10 transcription initiation site (CC10 region 1) have now been stud ied. This sequence can stimulate both in vitro transcription in H441 n uclear 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 re gion I. Transcription factors from H441 cells which are capable of bin ding 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.