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.
Frégeau
C J
CJ
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Helgason
C D
CD
Bleackley
R C
RC
D000818:Animals; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000201:enzymology*; D014162:Transfection / Q000235:genetics
D002087:Butyrates; D011993:Recombinant Fusion Proteins; D020148:Butyric Acid; D015500:Chloramphenicol O-Acetyltransferase; D012697:Serine Endopeptidases