FREAC-1 contains a cell-type-specific transcriptional activation domain and is expressed in epithelial-mesenchymal interfaces.

The forkhead transcription factor FREAC-1 is a potent transcriptional activator. We have localized a transcriptional activation domain in the C-terminus of FREAC-1 and another one to a stretch of approximately 60 amino acids in the central part of the protein. While the C-terminal activation domain activates in all cell lines tested, the activation domain in the central part of the protein is functional only in cell lines derived from lung. This cell-type-specific activity is retained when the activation domain is fused to the heterologous DNA binding domain of Gal4. The human FREAC-1 gene was found to consist of two exons separated by an intron of 1.2 kb. Exon 1 encodes the forkhead DNA binding domain and the cell-type-specific activation domain. Exon 2 encodes the general activation domain. The distribution of FREAC-1 expression during embryogenesis was investigated by in situ hybridization. FREAC-1 mRNA was found in mesenchyme in immediate proximity to endodermal epithelia throughout the digestive, urinary, and respiratory tracts. Mesenchyme surrounding the notochord and adjacent to the ectodermal epithelia of the oral cavity and developing teeth also expresses FREAC-1. The pattern of FREAC-1 expression, with highest levels in the mesenchyme next to the epithelium and gradually diminishing as the distance from the epithelium increases, suggests that FREAC-1 expression is a response to epithelial paracrine signaling and that FREAC-1 may play a role in epitheliomesenchymal interactions.