Expression of XXXX squamous cell differentiation marker, @entity56113 , in tracheobronchial epithelium depends on JUN and TRE motifs.

@entity1 @entity56113 @entity2755 @entity1178 @entity865 @entity864
Tracheobronchial epithelial (TBE) cells that normally do not express the squamous cell differentiation marker gene, @entity56113 , can be induced to produce it by @entity864 ( @entity865 ). The regulation of @entity56113 gene expression by @entity865 occurs, in part, at the transcriptional level in primary @entity1 and monkey TBE cells. Using a transient transfection assay, we observed that @entity865 stimulates the activity of the reporter gene, @entity2755 acetyltransferase, by 2-4-fold in transfected TBE cells. However, this @entity2755 acetyltransferase activity is cell type-specific with significantly less activity in transformed epithelial cell lines and no activity in non-epithelial cell types. @entity865 -dependent stimulation can also be demonstrated by co-transfection with plasmid DNAs that overexpress the JUN family of proteins, especially @entity1178 . Overexpression of @entity1178 and @entity865 treatment synergistically stimulate the @entity56113 promoter activity by more than 40-fold. Deletion analysis of the promoter region demonstrates that the DNA fragment of the first 98 base pairs of the 5'-flanking region contains the basal promoter activity, while the region between -162 and -96 contains the cis-enhancer elements for both the basal and @entity865 / @entity1178 -stimulating promoter activities. This observation is supported by in vivo genomic footprinting studies that reveal persistent protections in the following motifs of this region: -141 TRE, -131 GT, -123 ETS-like, and -111 TRE-like motifs and in the enhanced protections in -141 TRE and -111 TRE-like motifs in cells after the @entity865 treatment. Site-directed mutagenesis in this region demonstrates the involvement of both -141 TRE and -111 TRE-like motifs in @entity865 / @entity1178 -dependent stimulation as well as enhanced basal transcriptional activity. However, it is primarily the -111 TRE-like motif that is involved in the mediation of the enhanced basal promoter activity of the @entity1 @entity56113 gene. These results are further supported by gel mobility shift assays that demonstrate the involvement of @entity1178 and these TRE motifs in the formation of the DNA-protein complex.
