TRANSCRIPTION OF 2 CYTOTOXIC-CELL PROTEASE GENES IS UNDER THE CONTROL OF DIFFERENT REGULATORY ELEMENTS

Precursor cytotoxic T lymphocytes are activated upon interaction with antigen and interleukin 2. The development of the mature killer cell phenotype is achieved by the transcription of a number of function related genes including those encoding a family of cytotoxic cell proteases (CCP). Two of these proteases, CCP1 and CCP2 encoded by C11 and B10, are shown in this report to contain cell-specific transcriptional regulatory elements within their 5'-flanking regions. Two Positive regulatory sequences were mapped for C11 (-682 to -427 and -243 to -112) and one for B10 (-279 to -189). In addition each flanking region contains a region of DNA (B10 -1617 to -1049 and C11 -427 to -243) that has a negative influence on transcription. The positive regions do not appear to correspond to any previously characterized regulatory elements but do map to the same region as DNase I hypersensitive sites. When ligated to heterologous promoters these elements can still stimulate transcription but cell-specificity of expression is lost. In addition the combination of positive regulatory region and promoter is important for the stimulatory effect. The ability of these regulatory sequences to function and to determine cell-specific transcription does not appear to be an intrinsic property but also depends upon the context.