Two cytotoxic cell proteinase genes are differentially sensitive to sodium butyrate.

The 5'-flanking regions of two cytotoxic cell protease genes, CCP1 and 2, are sufficient to confer cytotoxic T lymphocyte-specific expression when fused to a reporter gene. The two regulatory regions are, however, differentially sensitive to treatment of the recipient cell, MTL 2.8.2, with sodium butyrate. With CCP1 a six-fold increase in cat expression was observed, whereas CCP2 was insensitive to the butyrate treatment. One major butyrate-sensitive regions was defined in the CCP1 5'-flanking sequence between -243 to -112 and another less effective one between-682 to -427. These fragments of DNA were also able to confer responsiveness to butyrate when ligated to a heterologous fos promoter. These sequences within the 5' flank of CCP1 share homology with other elements that have been defined as butyrate-responsive. We believe that our results argue against a pleiotropic affect of butyrate such as histone acetylation. More likely sodium butyrate is mediating a specific stimulation of transcription through modification of the activities of selected transcriptional regulatory proteins that in turn affect their interactions with proteins bound to the promoter.