Thyroid Transcription Factor-1(TTF-1) acts as a tissue specific transcription factor in the regulation of lung specific gene expression and as morphogenic protein during lung organogenesis. Currently, there is very little information on the cis-acting sequences and transcription and transcription factors that direct the TTF-1 gene expression. DNAse 1 hypersensitive (DH) sites represent a marker for active or potentially active chromatin and are likely to be especially important in gene regulation, being associated with many DNA sequences that regulate gene expression. It is clear that DH regions correlate with genetic regulatory loci and binding for sequence-specific DNA-binding proteins.

We have used DH site assays to identify putative distal regulatory elements in H441 lung adenocarcinoma cells, which express the TTF-1 gene and HeLa cells.

There are four DH sites 5' of the TTF-1 gene. These sites are located at base pair approximately +150, -450, -800, and -1500 from the start of transcription.

These data suggest that there may be at least one intragenic site and regulatory region 5' prime to the promotor region.