Truncation does not abrogate transcriptional downregulation of the c-myc gene by sodium butyrate in Burkitt's lymphoma cells.
We have examined the effect of sodium butyrate, a potent inducer of differentiation in various cell systems, on the steady state RNA level and transcriptional activity of the c-myc gene in Burkitt's lymphoma cells. Following sodium butyrate treatment a rapid decrease of c-myc RNA was observed in all Burkitt's lymphoma cell lines studied, irrespective of the type of translocation, the location of the breakpoint relative to c-myc or of the association with EBV. Since cellular genes induced by interferon are suspected to play a role in c-myc regulation we have studied transcription of the 2-5A synthetase gene in sodium butyrate-treated Burkitt's lymphoma cells. Transcriptional activity and steady state mRNA levels of the 2-5A synthetase gene were induced by sodium butyrate. The time course of induction excluded, however, that the decrease of c-myc RNA is caused by induction of the 2-5A synthetase/RNase L endonuclease system. The reduction of c-myc RNA is caused, at least in part, by a reduced transcription rate, as shown by nuclear run-on analysis. The fact that sodium butyrate is capable of downregulating a truncated c-myc gene indicates that an important target site of transcriptional regulation is located outside the region encompassing the upstream regulatory sequences, the dual promoters and the leader region.
Polack
A
A
Abteilung für Virologie, Universität Freiburg, FRG.
Eick
D
D
Koch
E
E
Bornkamm
G W
GW
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics; D002051:Burkitt Lymphoma / Q000235:genetics*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D009693:Nucleic Acid Hybridization; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
D002087:Butyrates; D012333:RNA, Messenger; D020148:Butyric Acid; D015088:2',5'-Oligoadenylate Synthetase