Truncation does not abrogate transcriptional downregulation of the c-myc gene by sodium butyrate in Burkitt's lymphoma cells

Abstract

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.